The Laboratory Mouse. Its Origin, Heredity
and Culture. Clyde E. Keeler, 81 pp. Harvard
University Press. 193 1.
A brief statement of the geographical distribu-
tion of the mouse is followed by an informing
account of the antiquity of the fancy mouse. It
appears that dominant spotting, albinism, and
waltzing were all recorded before the present era.
The other breeds were distinguished much later.
Since in the classical literature the same word
Mns was used for both the mouse and the rat, it
is only possible to determine which is meant by
the help of indirect evidence.
Some twenty-four breeds of mice are briefly
described and these descriptions followed by a
useful table, listing for twenty-seven varieties the
fanciers' term, the scientific term and the genetic
formula.
The genetics of normal and abnormal inherit-
ance are then considered, and the book closes with
a chapter on the laboratory breeding and care of
these animals.
Twenty-one life-size figures, in black and white,
indicate the habit and coat color in the several
breeds. — H. H. Donaldson.
Reviewed in the "Collecting Net"
August 8, 1931, by Dr. H. H.
Donaldson, and presented to the
Library or the Marine Biological
Labora tory
STUDIES IN GENETICS
GENETICS AND EUGENICS
OUTLINES OF A LABORATORY COURSE
IN GENETICS
THE GENETICS OF DOMESTIC RABBITS
REPRINT OF THE ROYAL HORTICULTURAL
SOCIETY'S TRANSLATION OF MENDEL'S
PAPERS ON PLANT HYBRIDIZATION
HARVARD UNIVERSITY PRESS
Cambridge Massachusetts
V
THE LABORATORY MOUSE
LONDON : HUMPHREY MILFORD
OXFORD UNIVERSITY PRESS
THE LABORATORY MOUSE
ITS ORIGIN, HEREDITY, AND CULTURE
BY
CLYDE E. KEELER, SC.D.
RESEARCH FELLOW OF THE HOWE LABORATORY
HARVARD MEDICAL SCHOOL
FELLOW BY COURTESY OF THE BUSSEY INSTITUTION
CAMBRIDGE
HARVARD UNIVERSITY PRESS
1931
%
COPYRIGHT, 1931
BY THE PRESIDENT AND FELLOWS OF HARVARD COLLEGE
PRINTED AT THE HARVARD UNIVERSITY PRESS
CAMBRIDGE, MASS., U. S. A.
CONTENTS
I. Introduction 3
II. Geographical Distribution of the House Mouse ... 4
III. Antiquity of the Fancy Mouse 7
IV. Unit-Characters (Gene Mutations) of the House Mouse 19
V. Normal Inheritance 35
VI. Abnormal Inheritance 44
VII. The Breeding of Mice in Laboratories 47
Bibliography 73
37949
ILLUSTRATIONS
PAGE
Fig. 1. The Egyptian Cat-goddess, Bubastis 8
2. Polychrome pottery mouse from Egypt 8
3. A. A coin of Alexandria Troas bearing the cultus statue of
Apollo Smintheus 10
B. A coin of Tenedos (300 B.C.) bearing the statue of Apollo
Smintheus and a mouse 10
4. The Japanese God of Wealth, Dai-koku, and his symbolic
white mouse 15
5. The mouse netsuke by the Japanese artist, Masateru ... 19
6. Diagram illustrating the inheritance of a simple, recessive,
mendelizing unit-character such as albinism 36
7. Diagram of a pair of chromosomes showing the linkage re-
lationship of two pairs of genes before, during, and after a
crossing-over 41
8. Diagram of a back-cross illustrating the linkage between rod-
less retina and silver pelage 42
9. Diagram of chromosomes of the house mouse with genes
for unit characters distributed arbitrarily among them to
show genetic independence or linkage of the characters . 43
10. Wire mouse cage used at the Bussey Institution 53
11. Sectional view of feeding can 57
12. Gray (wild coated) 59
13. Brown extreme dilute (bb cd cd) 59
14. Cinnamon chinchilla (bb cch cch) 59
15. Albino (cc) 59
16. Lethal yellow (A } 'A) .' 61
17. Non-agouti black (aa) 61
18. Sooty yellow (sable) (A r a) 61
19. Black-and-tan or white-bellied non-agouti black (at at) . . 61
20. Gray recessive spotted (piebald) (ss) 63
21. Non-agouti black with dominant spotting (aa Ww) .... 63
22. Japanese waltzer non-agouti black piebald (selected for
whiteness) (aa ss vv) 63
23. Non-agouti black-eyed-white (homozygous for piebald) (aa
Ww ss) 63
24. Blue or non-agouti dilute black (aa dd) 65
25. Non-agouti silver (aa ss) ^5
26. Non-agouti brown (aa bb) 65
vni ILLUSTRATIONS
PAGE
Fig. 27. Short-ear lilac or pink-eye non-agouti black short-ear (aa
pp se se) 65
28. Heterozygous naked ("nakt") (N?i) 67
29. Recessive hairless (hr hr) 67
30. Homozygous naked (NN) 67
31. Non-agouti dilute brown (aa bb dd) having developed two
large transplanted tumors 67
32. New-born mouse showing posterior reduplication. (Courtesy
of Dr. C. H. Danforth) 69
33. Non-agouti silver, normal and dwarf (2 1-2 months old (aa
si si) and (aa si si dw dtv) 69
34. Albino showing flexed tail 69
35. Skulls of mice showing normal and parted f rentals .... 69
36. Normal and rodless (rr) retinae of the house mouse ... 69
THE LABORATORY MOUSE
•
INTRODUCTION
Small rodents will always find a place in the laboratory of
the zoology teacher, the biological investigator, the medical
researcher, and the fancier. Each man has different problems
in mind: behavior, physiology, disease, and beauty among
others.
On account of certain innate qualities the house mouse,
Mus musculus, has become in many ways the laboratory
mammal most favorable for culturing. Its fertility, prolific-
ity, convenient size, short gestation period, its manifold
variations, inexpensive maintenance, resistance to open in-
fections, susceptibility to certain diseases, and ease of produc-
tion conspire to make it the laboratory animal par excellence.
The teacher of zoology uses variations of the house mouse
to demonstrate the laws of heredity, the biological investi-
gator employs them for physiological and genetic studies,
the advanced medical man uses them as media in which to
culture disease germs or for pathological tests as in the pro-
duction of sera, and the fancier prizes them for their aesthetic
appeal.
Literature upon the house mouse, its origin, history,
distribution, development, the nature of its variations,
the hereditary transmission of its varietal characters, and
methods of rearing it suitable for the needs of laboratories,
has not been assembled so far as I am aware. . The data are
in some instances rare, usually widely scattered, and often
inaccessible to those who could advantageously employ
them. Some are recorded in difficult and highly technical
language. Some of the data have never been published.
To collect such valuable information as this concern-
ing the house mouse and to present it in a usable form is
the task of this book.
II
GEOGRAPHICAL DISTRIBUTION OF
THE HOUSE MOUSE
The great order of Rodents or gnawing mammals is very
successful as judged by the extent of its distribution and the
degree of its adaptation to varied environments. Cavies
scuttle under brush, rats slink about human habitations,
mice squeeze through inconceivably small holes, squirrels
scurry up trees and leap or glide from branch to branch,
rabbits tunnel the earth, amphibious beavers fell trees and
build dams. Yet all are hopelessly dependent upon their
chisel-like incisors, which proclaim a common relationship
and give them a common name.
The five families of rodents enjoying the widest distribu-
tion (7) l are the Leporidse (rabbits, hares), the Hystricidse
(porcupines), Sciuridse (squirrels), Cricetidae (New World
mice, meadow mice, hamsters), and the Muridae (Old World
rats and mice having tubercular teeth).
Because the rabbits have four incisors in the upper jaw
and two in the lower, they have been assigned to the sub-
order Duplicidentata (duplex-toothed) or even made a
separate order, Lagomorpha. The porcupines, squirrels,
rats, and mice bear two incisors both above and below and
are placed in the sub-order Simplicidentata (simple-toothed).
Of these successful families the last two have attained
world distribution, while the other three had established
themselves before modern times in all geographical regions
except the Australian.
The accepted classification of the common house mouse is :
Order Rodentia (gnawing animals)
Sub-order Simplicidentata (simple-toothed)
Family Muridre (mouse-like animals)
Genus Mus (true mice)
Species musculus (the little mouse)
1 Italic figures in parentheses refer to names listed numerically in the Bibliog-
raphy at the end of the text.
4
GEOGRAPHICAL DISTRIBUTION 5
The ancestral house mouse, from the present-day species
of which the main breeds of the fancy are derived, is un-
doubtedly of Central Asiatic origin. The date of its first
appearance in Eocene times and its subsequent expansion
may only be conjectured in terms of numerous millennia.
From the region of its early development it made its way to
the habitable portions of Europe, Asia, and northern Africa,
perhaps often as a stowaway in early human migrations.
At the present time the species Mus musculus is represented
in the old world by several interbreeding species and their
natural varieties. In northern Africa and Syria the pale,
white-bellied M. musculus gentilis is found. M. musculus of
southeastern Europe is in general darker than that of north-
ern Europe, and it seems to be the darker animal that be-
came established in Mexico and South America through
colonization by South Europeans, whereas the lighter form
is more common in the United States and Canada.
The Asiatic Mus bactrianus group is lighter and more deli-
cate than the European M . musculus, but breeds freely with
it. Fancy breeds of mice often partake of blood of both
types, while the Japanese waltzing mouse of the fancy may
be derived (158, 59) solely from the bactrianus of China or
Tibet.
Mus bactrianus (or wagneri (55)) ranges from Persia to
China. The general type of bactrianus blends into the short-
tailed M. bactrianus gansuensis of Mongolia and into the
long-tailed M. bactrianus kakhycncnsis in Indo-China and
the Malay peninsula (4).
The species Mus musculus proper shared with the Euro-
pean his recent conquest of the globe, and was uninten-
tionally transported on ships or among merchandise to all
habitable regions including the Asiatic seacoast normally
within the range of the bactrianus group.
This internationalization of the mouse has been so recent,
and complete isolation has been so rare, that few distinct
varieties have been able to develop and persist as such in
nature. However, where some isolation has been afforded,
6 LABORATORY MOUSE
several color varieties have maintained themselves distinct
for many years. For example, a white-bellied colony of mice
has been found near Woods Hole, Massachusetts (13Jf.) ; in
a region in northern France the black (non-agouti) form has
become the sole house mouse to the exclusion of the normal
gray variety; the Isle of Wight off the coast of England is
populated with the pink-eyed variation.
The present universal supremacy of M. musculus or
M. bactrianus as house mouse is challenged only in very
circumscribed localities where the white-footed field mouse
occasionally supplants it. The largest such area is thought
to be southern Persia, where Apodemus sylvaticus takes its
place.
Ill
ANTIQUITY OF THE FANCY MOUSE
Variations of the word "mouse" found today in many
European languages go back through the Latin mus and
Greek mus or mys to mush in Sanscrit (100), the mother
tongue of the race. In Sanscrit mush is derived from a verb
meaning "to steal." This suggests that man was well
acquainted with the mouse and its predatory habits before
the separation of the Aryan tribes in Asia some four thou-
sand years before Christ. One of the old Zoroastrian legends
says that the moon chases away the clouds as a cat (weasel?)
chases mice.
Rats and mice abounded in the ancient world from earliest
times, especially where grain was stored. There are numer-
ous historical accounts of excessive increase of these rodents
constituting veritable plagues in ancient civilizations, some-
times accompanied by disease (138).
Stories of rats and mice became early incorporated in
the folklore of the ancient world along with anecdotes about
their enemies the cat and the weasel. A specific word for
house mouse as well as legends concerning it exist today in
nearly every human dialect.
In Egypt. The fact that rats and mice appear so rarely
in Egyptian art is probably due to the fact that they were
considered undesirable animals, and for this same reason
the Nubian cat, as a destroyer of rats and mice, was deified
before the Third Dynasty (c. 2800 B.C.).
The sacred cat Bubastis (see Fig. 1) was not only the
patron goddess of the prosperous delta city of Bast, but also
the goddess of love and feminine fashion. Iphthimis her son
was the god of goodness. In the holy city of Bast stood the
famous cat mausoleum, where the remains of sacred felines
were ceremoniously laid to rest in bronze or wooden cat-
8
LABORATORY MOUSE
shaped coffins. Each year Lower Egypt thronged to the
riotous feast of Bubastis, and families went through a mourn-
ing ritual for their deceased cats similar to that
for human members of the household. Since
the cat embodied all godly virtue, the mouse
probably came to symbolize evil by contrast.
Indeed, it may be suggested that rats and
mice were probably responsible to a great de-
gree for the cat's deification, because the Nile
delta has been a grain-growing region since
prehistoric times, and was undoubtedly over-
run with these rodents before the advent of
the cat from Nubia.
A glazed polychrome effigy of a white-
bellied agouti mouse made in Egypt 2000
B.C. is in the British Museum (see Fig. 2).
A satyrical papyrus of the New Kingdom
(153) (written between 1580-1205 B.C.) bears
the picture of a rat or mouse (possibly Mus
cdexandrinus) in kingly robes, attended by Egyptian cats.
Aelianus (c. a.d. 100) remarks that in Lower Egypt mice
develop from raindrops. St. Basil (a.d. 330-379) repeats the
story of pluvial generation of mice in Egypt, but adds grass-
hoppers and frogs as co-creations.
Fig. 1. The Egyptian
Cat-goddess, Bubastis,
redrawn from Keller
after Perrot-Chipiez.
Fig. 2. Polychrome pottery mouse from Egypt, c. <2000 B.C.
(In British Museum.)
In Palestine. Moses received his cultural training in Egypt
and with it the traditional hatred for mice. This attitude
is exemplified among the commandments to the Hebrews
recorded in the Book of Leviticus:
ANTIQUITY OF THE FANCY MOUSE 9
These also shall be an abomination to you among the creeping things
that creep upon the earth; the weasel, and the mouse, and the tortoise after
his kind. . . . These are unclean to you among all that creep: whosoever
doth touch them, when they be dead, shall be unclean until even.
In the Old Testament is an account of a rat or mouse
plague accompanied by intestinal disease which was brought
upon the Philistines about 1000 B.C. following the seizure
of the Israelitish "ark of the covenant." Golden effigies
both of mice and of the affected portions of the human
anatomy were given as gifts to Y'ahweh in order to appease
his wrath.1
In Asia Minor. Probably the first recorded instance of
the raising and protection of mice by men is in connection
with the ancient mouse worship of Pontis instituted perhaps
some fourteen hundred years before Christ. Homeric legend
(c.1200 B.C.) mentions Apollo Smintheus (god of mice). This
cult was popular at the time of Alexander the Great (300
B.C.).
During the latter part of the second millennium before
Christ, Cretan Teucri invaders landed upon the shore of
Asia Minor for the purpose of colonization. For a long time
they were restricted to the coast by the aboriginal Pontians,
with whom they continuously contested in arms. A decisive
victory for the Cretans was credited to the mice (probably
field mice), which their Apollo caused to gnaw the leather
straps from the shields of the enemy (65).
Several Greek and Roman historians (1, 163) describe in
some detail the temple which the conquering Teucri erected
upon the Pontic island of Tenedos in gratitude to Apollo,
god of mice. Tradition has it that before the Teucri set out
from Crete they had been given an oracle commanding them
that where they settled there they should build a temple
1 Herakles Kornopion, the Tyrian Sun god as well as Baalzebub (harmonized
by the Greeks as the Fly god Zeus) frequently bears the mouse symbol. On a
Carthaginian votive stone described by Vigouroux-Ibach are carved two mice as
gifts to either Baal or Astarte-Aphrodite. Herodotus says that the statue of Seti
III within the temple of Ptah at Memphis had a mouse on the hand and bore the
inscription: "Look on me and be just!" (100)
10 LABORATORY MOUSE
to Apollo and worship the "earthborn creatures." The
foundation of this temple was still standing in 1902. The ac-
counts picture vividly a magnificent marble shrine overrun
with sacred mice which were raised at public expense. They
describe the altar, tripod, and statue of "Apollo, God of
Mice." He stands stiffly in the style of the archaic Greek
period. In his right hand he holds a patera, in his left he
Fig. 3.
A. A coin of Alexandria Troas bearing the cultus statue of Apollo Smintheus. (Natural size.)
B. A coin of Tenedos (300 b.c.) bearing the statue of Apollo Smintheus and a mouse.
(Enlarged about 3 diameters.)
carries a bow. At his feet is the huge effigy of a mouse, while
a family of white mice have their nest under the altar itself
(see Fig. 3).
A priestess of this temple, Herophila by name, was said to
have correctly interpreted Queen Hecuba's dream concern-
ing the fall of Troy and the fate of herself and family.
The mouse cult (56, 169) spread from Tenedos to Alex-
andria, Hamaxitus, Larissaia, Parion, Heraclea, Grynaeus,
and Chryse in Asia Minor, and the god was even honored in
Lesbian Arisba, Methymna, and Magnesia. Record of the
cult is to be found in Athens and Thespia on the Greek main-
land. In some of these centers it probably continued as a
local form of worship until the Turkish conquest in 1453.
Thus the Sminthian worship existed for about three thousand
years and white mice were cultured in the temples for about
two thirds of this period, mainly for auguries.1
1 Jamblichos is authority for the statement that mice were employed for augu-
ries in Babylon, while Aelianus mentions the soothsaying rites of Apollo Smintheus
(100).
ANTIQUITY OF THE FANCY MOUSE 11
Coins of the Troad, and especially Alexandria Troas, fre-
quently bear the figure of the cultus statue and in several
instances the sacred mouse (41) -1
Aristotle refers to the white mice of Pontis. Strabo (c. 25
B.C.) (163) mentions the white mice cultured in the many
Sminthian temples. Pliny (c. a.d. 25) (150) alludes to the
use of white mice for auguries. White mice are mentioned
by Aelianus (a.d. 100) (1), Hesychius (c. a.d. 500) (100),
Suida (1100) (65), Albert (1250) (65), Apostolius (1453)
(65), Gesner (1560) (65), Johnson (1640) (84), Pallas (1766)
(143), and Darwin (1865) (36), while more recently the au-
thorities writing upon them have been too numerous to
mention.
Pliny says in this connection:
And verily, how basely men thinke of this kind of eattell and hold them
no better than vermine, yet are they not without eertaine naturall prop-
erties, and those not to be despised : but principally in regard of the sym-
pathy between them and the planets in their ascent, I have noted hereto-
fore: and namely, considering how the lobes and filaments of their livers
and bowels do increase or decrease in number according to the dais of the
Moon's age. . . . By the learning of soothsayers, observed it is, that
if there be a store of white ones bred it is a good signe and presageth
prosperitie. — Translation of Philemon Holland, 1635.
The pharmaceutical virtues of the mouse so often em-
ployed by Greek and Christian doctors may be attributable
in part to the influence of the mouse cult of Pontis.
Greece and Rome. The Homeric story of " Batrachomyo-
machia" or the "Battle of Frogs and Mice" probably origi-
nated in Ionia about 750 b.c. An analagous story was
popular in Europe during the early Christian centuries. The
latter tale was known as Galliomyomachia ("The Battle
of Weasels and Mice"), and describes a war waged by the
weasels upon the rats. The story may have been occasioned
by the influx into Europe of the black rat (Rattus rattus)
following the migration of the Germanic tribes, which animal
finally gained a foothold in England during the fifteenth
century. .
1 Coins of Nesos, Lampsakos, Nagidos, and Metapont bear a mouse.
12 LABORATORY MOUSE
Aristotle (300 b.c.) said that mice were generated spon-
taneously from filth in houses and in ships. Horace (65-8
B.C.) wrote the famous story of the Country Mouse that
returned a visit to his cousin the Town Mouse. Pliny (a.d.
23-79) in his Historia Naturalis classified the different kinds
of mice, calling the house mouse "musculus" (little mouse),
which name it bears today in zoological taxonomy. Pliny
also recorded that the ashes of a weasel sprinkled about the
house will keep away mice. He stated that in Ionia mice
are generated by the overflowing of the Meander River,
even causing the inhabitants to flee from their dwellings. He
told of the driving out of the entire population of the Isle of
Gyarus by mice which proceeded to gnaw the gold, iron, and
steel left behind.
Europe. In Christian Europe mice and rats fell into dis-
repute, becoming the companions of witches and sorcerers.
This was partly due to the attitude of the Church following
the condemnation of these creatures by Moses.
The clergy of the Middle Ages never ceased to comment
upon the voluptuous and libidinous habits of mice. Indeed,
mice were frequently raised by curious churchmen in order
to observe their wicked actions. Albert (65) records that the
white ones are very lustful. In this statement he follows
Diogenes. Gesner (65) says they are libidinous. Erasmus
records their lust.1 Part of the European attitude may have
been due to plagues and current legends originating in Greek
mythology.2
Horace (65 b.c.) spoke of the mountains being in labor and
bringing forth a "ridiculus mus," which is to this day a
proverb of futile effort. Aelianus calls them "earthborn
creatures." 3 About a.d. 1500 Erasmus collected together
1 The mouse was often a symbol of delicacy or lust in Greek drama. In the
British Museum is a bronze mouse from Iconia which holds over its face the mask
of a Silen, a creature usually represented as a man having a horse's tail, and the
symbol of lust in the worship of Dionysos.
2 The ancient Persians and Bactrians held that mice were creations of the
wicked god Ahriman.
3 A Talmudic fable speaks of a mouse in the process of creation, the fore parts
already flesh and the hinder parts still earth.
ANTIQUITY OF THE FANCY MOUSE 13
some eight hundred legends, a number of which were reputed
to be the works of Aesop (c. 620-560 b.c). According to
Erasmus this brand of murine-generation story was origi-
nated by Aesop and copied by Porphyrion (a.d. 233-304),
who gives the following account (65) :
As once when wild and uncivilized men saw the earth to heave up and
move in a mountain, they ran together from every direction to such a
dreadful sight, expecting that the earth would there give forth some new
and great spectacle (the mountain indisputably laboring). Perhaps it
should be that the Titans would burst forth again and renew their war with
the gods! Then, while all the multitude stood there in suspense with
astonished spirits, a mouse broke out of the earth, and a laugh arose from
all the people.
Plutarch (a.d. 46-120) says that mice conceive by licking
salt. He copies this from Aristotle, who not only believes in
the saline method of engendering but records a ridiculous
litter size of one hundred and twenty young produced
through this kind of parthenogenesis. This story was brought
to Aristotle by a veteran of Alexander's military campaign
in India, who apparently wished to impress the old naturalist
with the marvels of that far-away land. Thomas of Can-
timpre (c. a.d. 1228-1244) avers that the size of mouse livers
waxes and wanes with the moon, but in this he repeats Pliny.
These legends expanded to their greatest proportions dur-
ing the Middle Ages when mice along with other base
creatures were considered the handiwork of devils. Casper
Schott (a.d. 1697) (156) in his interesting Physica Curiosa
is bold enough to suggest that diabolical assistance may not
be necessary in the creation of lowly animals as commonly
believed, because many of the forms are known to be pro-
duced by spontaneous generation. He says:
The first reason for doubting is because many animals arise from putrid
material and by other means without the intervention of father and
mother. . . . Indeed, agile boring larvae and little worms are given birth
in rotting wood; from putrefaction slugs, snails and mice, from ox dung
honey bee drones and wasps; from the aerated urine of caterpillars, butter-
flies, ants, grasshoppers, cicadas and other similar- forms.
In this tale he follows Pliny, who in turn copies it from
Aristotle.
14 LABORATORY MOUSE
The reputed parthenogenetic reproduction of the mouse
was held up by the clergy as an example of the natural-
ness of human parthenogenesis demanded by Christian the-
ology.
Before the advent of the Persian cat into northern Europe
during the time of Charlemagne, mice and rats frequently
multiplied in such numbers that they could not be kept in
check by the weasels maintained by the more fortunate
families. These conditions gave rise to such stories as that
of the Pied Piper of Hamlin.
The early Greek and Roman physicians employed mice
in their medicinal formulae. Hippocrates (300? B.C.) says that
he did not test the virtue of mouse blood as a cure for warts,
prescribed by his colleagues, because he had a magic stone
with lumps upon it which had proved an efficient remedy.
Galen (a.d. 130?-c200?) advocates equal parts of mouse
blood, cock's gall, and woman's milk mixed and dried as a
cure for cataract. Villanova uses dog's urine and mouse
blood for warts.
During the Dark Ages the formulae became increasingly
occult and complicated, and mice figured even more in the
pharmacopoeia.1 St. Hildegarde of Bingen (1098-1179) re-
counts that mice are a cure for epilepsy. The manuscript
known under the name of Picatrix (ll2o6) endorses fumigation
with fourteen bats and twenty -four mice. Peter of Albano
employs mouse dung as a cure for poisons, probably in-
fluenced by Pliny's freshly killed mouse poultice for serpent
bites.2
1 The mouse seems to disappear from medical formula? during the latter part of
the seventeenth century, although crab claws and millipeds persist even in the
literature of the last century. The London Pharmacopoeia {161/) of 1667 instructs
as follows: "A flead mouse dried and beaten to powder, and given at a time, helps
such as cannot hold their water or have Diabetes, if you do the like three daies
together." The influence of this dictum was felt at Boston, Massachusetts, as late
as 1890, when a family of English extraction fed mouse stew to their children to
prevent bed-wetting.
2 In Europe mice used to be eaten as a remedy for toothache. New-born mice
dissolved in olive oil are a popular panacea for human ills in Turkey and Greece
today.
ANTIQUITY OF THE FANCY MOUSE
15
The Orient. Although until recently the house mouse has
been openly despised by Christian teachers, in the Orient,
on the contrary, it has always enjoyed a much higher social
rating.
Albino mice were used by the Chinese priests for auguries
and during many centuries the government preserved records
of their taking in the wild. These records cover the period
Fig. 4. The Japanese God of Wealth, Dal-koku, and his symbolic white mouse.
(After a print in the Museum of Fine Arts in Boston.)
between a.d. 307 and a. d. 1641. During this time the finding
of about thirty albino mice was recorded by the magistrates.
From Turkestan to Japan, years are reckoned in cycles of
twelve, the first year of each cycle being named the "Mouse."
In Japan the mouse of the folk-sagas is a very wise creature
and the symbol and messenger of the God of ^Yealth, Da'i-
koku (see Fig. 4). The god is usually represented as stand-
ing upon two sacks of rice with a mouse perched at his feet.
The time between 11 p.m. and 1 a.m. is known as the hour of
the mouse. A children's story describes the wedding of the
16 LABORATORY MOUSE
mice.1 Thus national tradition provided a psychological
attitude among the Japanese most favorable for the develop-
ment of the mouse as a fancy animal. In Japan today the
mouse fancy is well developed, having thriven for at least
three centuries.
It is difficult to ascertain how long varieties of the house
mouse have been recognized in China. The word for white
mouse is ancient, and that for spotted mouse appears in the
earliest Chinese lexicon, written 1100 B.C. The waltzing
variety has been known since 80 b.c. That the Nipponese of
Yokohama and elsewhere zealously collected new varieties
in foreign lands is shown by the fact that they call a mouse
bearing certain markings the "Nanking Mouse" (162),
while the Chinese fanciers of Shanghai near Nanking deny its
origination and call it the foreign mouse. The Japanese
waltzer was undoubtedly derived, at least in part, from Mus
bactrianus (wagneri) of Tibet, as pointed out by Bowdler
Sharpe (158) in 1912. Moreover, Mus musculus proper is not
native to Japan. Perhaps the Japanese procured the Euro-
pean M. musculus varieties from Portuguese traders.
The Japanese had in their fancy such varietal characteris-
tics as albinism, non-agouti, chocolate, waltzing, dominant
and recessive spotting, and possibly blue dilution, pink-
eyed dilution, and lethal yellow.
Something over a hundred years ago several of these
fancy varieties of the house mouse were taken from Japan
to Europe by British traders, and only a few decades ago did
muriculture spread to America.
During the nineteenth century a number of European
zoologists bred fancy mice for scientific investigation of the
inheritance of varietal characters. They accumulated valu-
able information, but the meaning of these data remained
unknown until the rediscovery of Mendel's Law of Heredity
in 1900 (33).
1 The Japanese have a saying that white mice are good and honest while dark
ones are wicked and dishonest. Believing that good overcomes evil, some Japanese
bring white mice into their houses in order to drive out the wild gray ones.
ANTIQUITY OF THE FANCY MOUSE
17
The essential feature of this law is the fact that the charac-
teristics which differentiate domestic varieties are inherited
as units, capable of being combined in all possible ways
through the agency of hybridization. Up to the present time
about two dozen such unit-characters have been recorded
for the house mouse. The more important of these appear
to have been first recorded at dates approximately as follows :
Character
Date
Authority
B.C.
Dominant spotting c.1100
Albinism 300
Waltzing 80
A.D.
Pink-eye dilution 1640
Black 1640
Recessive spotting (piebald) 1766
Chocolate 1843
Naked (dominant hairless) 1850
Chinchilla c.1890
Extreme dilution c.1890
Yellow 1902
Blue 1903
Short ears 1921
Rodless 1924
Recessive hairless 1926
Shaker 1926
Hyperglycemia 1926
Dwarf 1929
Eh Yah
Aristotle
Annals of Han Dynasty
Johnson
Johnson
Pallas
Gray
Gordon
Blake
"An old fancier"
Cuenot
Bateson
Lynch
Keeler
Brooke
Lord and Gates
Cammidge and Howard
Snell
In accordance with our present ideas, each unit-character
made its appearance as a sudden, discontinuous physical or
chemical change in the germinal substance, which forms the
basis of heredity. We call such changes mutations, and the
material bodies in which these changes occur are called
genes. We can demonstrate the existence of a gene only
when, as a consequence of mutation, it occurs in two differ-
ent alternative forms in different individuals of the same
species. By crossing individuals which bear different allelo-
morphs of the same gene, we can show that transmission of
the contrasted characters conforms with Mendel's Law.
18 LABORATORY MOUSE
Each unit-character is borne in or determined by a differ-
ent gene, and is independent in its transmission of every
other gene, except such as lie in the same chromosome with
itself, a complication resulting in genetic linkage, a phenome-
non to be more fully discussed later.
IV
UNIT-CHARACTERS (GENE MUTATIONS)
OF THE HOUSE MOUSE
The Japanese, as already stated, must be given credit for
the development of a number of varieties of domestic mice.
An ivory netsuke or sash pendant in the Louvre {155) carved
about 1790 by the Japanese artist Masateru depicts a family
of fancy mice in natural color among which one may dis-
tinguish the unit-characters pink-eye, piebald, non-agouti,
albinism, and waltzing (see Fig. 5). Similar netsukes were
popular during the nineteenth century.
Fig. 5. The mouse aetsukl by the Japanese artist, Masateru.
(After a photograph hy Schluruberger.)
We have reason to believe that each unit-character arose
by mutation or physical change in a particular gene located
in a particular chromosome of a germ cell, and that this con-
dition was transmitted to subsequent generations through
heredity, the character manifesting itself in those individuals
which carried certain hereditary combinations.
We may also be confident that identical sports have arisen
in the wild at different times in remote parts of the world.
Among the stuffed skins of the house mouse in the British
Museum collections in 1926 were found pink-eyed dilutes
from the Isle of Wight off the coast of England and from
Zanzibar (the same variety was recently taken in the wild in
Germany). Albinos had been collected from numerous locali-
20 LABORATORY MOUSE
ties. Several pied mice were listed from Syria. Blue-dilute
specimens came from Esthonia and Syria, non-agouti (black)
specimens from Cape Colony and England. Cinnamons were
taken in South Africa and the Tigris Valley. There were
white-bellied agoutis from Syria and Persia. Several speci-
mens from West Africa probably contained extreme dilution.
The mice were all taken in the wild and not purchased from
fanciers. These facts refute the common belief that the
varietal characteristics found in fancy stocks are the results
of domestication. The natural cause which produces such
mutations in the germ cells is as yet undiscovered. Under
laboratory conditions /3-rays of radium and X-rays are able
to produce in the fruit fly (Drosophila) mutations identical
with those appearing in this species in nature (139). It is
possible that cosmic rays in nature are responsible for the
origin of some of the house-mouse variations.
Myriads of mutations may arise and be lost in nature
without ever being seen by man. Where accidentally a
mutation has struck the fancy of man, he has secured and
propagated it in captivity, selecting in the following genera-
tions for the particular character in question. Where a
mutant form arises in any one of the thousands of labora-
tories breeding mice today {113, 71, 160, 146), it is quite
likely to come to the attention of man and be preserved.
Thus the number of mutants recorded as found in the wild
is not comparable with the number observed to have origi-
nated in laboratory stocks nor is it legitimate to conclude
that the mutation rate in captivity is greater than that in
the wild.
Gray (normal wild coat). The gray coat (4U2) of a wild house
mouse (see Fig. 12) is produced by the deposition of two
kinds of pigment (yellow and black) in different portions of
the hairs. Yellow is present normally in an apical or sub-
apical band of many of the hairs. In general upon the
ventral pelage the band becomes wider and the black pig-
ment less, giving the belly a distinctly lighter appearance
than the back. These pigment differences may be due to
UNIT-CHARACTERS (GENE MUTATIONS) 21
different types and rates of pigment production in the hair
follicle, with an inhibitor for the black process when the
banded region is forming. Chocolate pigmentation which
takes the place of black in some fancy varieties may be
looked upon as a condition in which the black reaction has
been checked in an early phase.
Albinism (c, mutant form of the color gene, C).
The white mouse of Pontis is said to ruminate. — Aristotle, 300 B.C.
Complete albinism (see Fig. 15) is a condition in which
pigmentation is entirely wanting in all parts of the body. Not
only are external organs devoid of pigment but even those
internal regions which normally develop pigment, such as
the eyeball and the outer surfaces of the brain and spinal
cord, are unpigmented. Animals bearing albinism have
white hair and pink skin. The eye color is usually either
pink or whitish according to whether or not the retinal blood
supply is visible through the iris. Histological examination
reveals the fact that in albinos pigment granules are present
which are normal in shape and distribution, but which are
leucotic.
A common explanation (140) for the production of albi-
nism is the absence of the colorless tyrosinase, which ferment,
working upon the base or substrate, tyrosin, converts it into
the pigment melanin. Several chemical reactions are in-
volved in the process. Some maintain that it is the tyrosin
which is lacking in albinos. This assumption appears more
probable in view of the allelomorphic series of dilutions
produced by different forms of the albino gene.
The gene or hereditary determiner for albinism in the
mouse is the lowest step in a series of alternative chemical
states possible for this particular gene. The other states of
this gene produce respectively normal pigmentation (C),
chinchilla (cch), and extreme (Himalayan) dilution (c11).
A corresponding complete series of allelomorphs is found in
rabbits. Albinism in crosses (18, 69) behaves as a recessive
22 LABORATORY MOUSE
to normal pigmentation, chinchilla {157), and extreme dilu-
tion (39).
Complete albinism or one of its allelomorphs in which
very little pigment is produced is known to occur in fish,
birds, and most species of mammals, including man.
Extreme Dilution (cH)
Mr. J. E. Knight brought into my laboratory a young male mutant
mouse which he had captured in a corn crib. . . . This animal . . . gave
the appearance of being an ordinary black eyed white in which the hair
was apparently very slightly stained or dirty. — Detlefsen, 1921.
The above description of the extreme-dilute mouse (see
Fig. 13) is quite accurate (39). These animals vary in shade
but are always a dirty white color. This is apparently due to
a complete suppression of yellow and an almost complete
suppression of black and brown in the coat. I have found
that intense pigmentation persists in the ears, eyes, upon
the tail, and to a lesser degree upon the feet.
In the possession of pigmented extremities this mutant
resembles Himalayan albinism of the rabbit, and indeed its
determiner occupies a corresponding position among the
alternative forms of the albino gene.
Upon superficial examination of extreme dilutes it is im-
possible to distinguish blacks, browns, agoutis, non-agoutis,
and so forth. Closer inspection and continued handling en-
ables one to differentiate blacks from browns by the shade
of pigment upon the ears. These distinctions may be con-
firmed by clearing the irida? in xylol. Such prepared iridse
show normal black or chocolate pigmentation according to
whether the animal is genetically a black or a brown.1
Chinchilla (cch)
Thus the first generation of hybrids (between wild gray house mice
and fancy albinos) consisted of 342 mice, of which 329 were gray, seven
yellow and six chinchillas. — - Schuster, 1905.
1 An old fancier in the fourth edition of Fancy Mice says: "Occasionally impure
breeds and strains (of albinos) are raised in which there are black ears, eyes, and
feet. . . ." This may indicate extreme dilution, which being a dominant allelomorph
to true albinism might carry it as a recessive and continue to produce true albinos
generation after generation.
UNIT-CHARACTERS (GENE MUTATIONS) 23
The chinchilla mouse with black agouti coat may be
described (157) as a bluish gray containing no yellow, its
pelage resembling closely that of the gray squirrel. Brown
agouti animals containing the chinchilla factor (see Fig. 14)
are easily distinguished by their brownish coat, with white
rather than yellow bands of the agouti distribution pattern.
Chinchilla has a tendency to remove yellow from the coat,
although it also dilutes black and brown pigments, changing
non-agouti black to sepia. This leaves parts of agouti hairs
almost white and the bellies of agouti chinchilla animals are
usually quite colorless.
The yellow-reducing tendency is easily demonstrated by
the fact that when lethal-yellow mice are crossed with
chinchillas and yellow animals are produced carrying two
doses of chinchilla, these animals have a cream coat and
black eyes.
Chinchilla (157, 57) of the mouse corresponds to chin-
chilla of the rabbit both in appearance and genetic behavior,
being in both cases produced by a form of the albino gene
recessive to normal pigmentation and dominant to both
extreme dilution (Himalayan) and true albinism.1
Pink-eyed dilution (p)
Scaliger saw another (mouse) very bright, with flaming eyes. — John-
son, 1640.
This mutation (see Fig. 27) reduces greatly the black or
brown pigment, giving the eye a beautiful pink tint, from the
color of the blood in the eyeball. The coat of the agouti
black is changed to a fawn. The coat of the agouti brown
(cinnamon) becomes also a fawn but more brilliant than the
pink-eyed black agouti, because brown pigment replaces
1 Dr. C. Carter Blake (Fancy Mice, fourth edition) in a letter written about
1890 describes two crosses in which albinos mated with albinos produced colored
young. His results may be explained if it be assumed that the male used was really
a synthetic albino homozygous for pink-eye, heterozygous for non-agouti, brown,
and spotting, and bearing one dose each of chinchilla and albinism. If this be the
true explanation of these crosses, then human experience with chinchilla antedates
Schuster's crosses in which chinchilla came in heterozygously from a gray mouse
caught in the wild.
24 LABORATORY MOUSE
black. Pink-eyed dilution (32, 23, 19, 5Ji) changes non-
agouti black to "lilac" and transforms chocolate to "cafe au
lait."
That pink-eyed dilution works only upon black and brown
pigment is demonstrated by the fact that the coat color of
lethal yellow is almost unchanged by the addition of pink-
eyed dilution although the black eye of the lethal yellow is
changed to pink.
Non-agouti (a)
As to color, many are like the ass; however some are einerous, others
even black, others from brown to red. — Johnson, ] 640.
Non-agouti (see Fig. 17) is due to a mutation resulting in
loss from the individual hairs of the normal banded distribu-
tion pattern determined by the gene A. No yellow apical
band is formed in the non-agouti animal, but the black or
brown pigment extends the full length of the hair. Absence
or inactivation of the agouti gene (A) in the mutant type
non-agouti (53, 54) (aa), changes a gray mouse to black and
a cinnamon to rich chocolate.
Lethal yellow (Ay)
In my cultures I found in addition yellow mice. ... — Cuenot, 1902.
Presence of the yellow mutation (see Fig. 16) in a mouse
is easily recognized by its brilliant yellow coat and jet-black
(or brown) eye. These effects are due to the complete or
nearly complete suppression of black pigment, save in the
eye. In the eye of a yellow mouse black pigment is even
more abundant than in that of a black mouse, as proven by
clearing specimens of both types in xylol.
Yellow is a dominant character, i.e. it requires but one
dose of the gene to cause the animal to exhibit the character.
Animals containing two doses of the yellow gene (homozy-
gotes) are inviable (15, 24, 10^, 20, 79). Thus, as the yellow
gene is an allelomorph to the agouti (166) (A) and non-
agouti (a) genes, a yellow mouse will contain one dose of
yellow and one of either agouti or non-agouti (A1 A or A* a).
UNIT-CHARACTERS (GENE MUTATIONS) 25
Those yellows which contain a non-agouti gene (a) are
often sooty yellow (see Fig. 18) in appearance, and have
sometimes been called "sables" (47, 54)-
Chocolate yellows are clearer in color than those contain-
ing black, i.e. have a less sooty appearance.
Reds (AYA, or YYa plus darkening modifiers)
These animals of the fancy are a dull red, similar in color
to Rhode Island Red fowls.
Genetically they are lethal yellows with intensifying modi-
fiers. They breed as yellows, but the complete genetics of the
modifiers has not yet been worked out, although Dunn (46)
has studied it extensively and has shown that it must be
considered as due to numerous modifying genes.
Dominant spotting (IF) (broken spotting)
A mouse with the hair pattern of a leopard. — Eh Yah, c. 1100 B.C.
This variety (see Fig. 21) is characterized by the presence
of small irregular broken spots or polka-dot patches of color
upon a white ground. In higher grades pigmentation per-
sists about the eyes and dorso-caudal region only.
Dominant spotting (112, 162, 53, 72) is expressed, as the
name indicates, in animals containing but one dose of the
gene. Homozygotes die of anaemia at an early age, under
eighteen days (37, 40). Fancy breeds of this type are known
as black-eyed whites (see Fig. 23). They contain one domi-
nant-spotting gene and two recessive-piebald genes, i.e. are
heterozygous for dominant spotting and homozygous for
recessive piebald. In some strains, perhaps all, pure-breds
(homozygotes) are inviable. Dominant spotting may be
due to localized inhibitors for the tyrosin-tyrosinase reaction.
This type of spotting has come to us from Japan. In Chinese
history it is recorded that in 120 b.c. (or more probably
a.d. 40) a wise court official who was able to recall the name
of this variety was rewarded by the Emperor with a cartload
of silken textiles.
26 LABORATORY MOUSE
Recessive spotting (s) ("piebald")
I have seen indeed a gray variety with a white saddle and also a white
varietj7 spotted with black. — Pallas, 1766.
In this type (see Fig. 20), large unbroken areas of white are
present upon the belly, back, and face (3). There is a tend-
ency to form a white belt and a white face. Recessive spot-
ting (61) in its highest grade usually leaves two patches of
pigment about the ears, the rest of the coat being white.
This is the condition usually found in the Japanese waltzing
mouse (see Fig. 22) . Additional pigmented spots when present
are usually found upon the rump. Animals bearing but one
dose of the higher grades of spotting often have a small
belly patch of white, but are otherwise colored. It is possible
by systematic selection to produce strains with white faces
or belts (50). What has been said concerning the probable
immediate cause of dominant spotting (tyrosintyrosinase
inhibition) applies to recessive spotting as well.
Yellow belly (Aw, a1) (white belly, light belly)
The back is a gray tinged with red-brown, the belly is bordered with
red-brown: the exact livery of the field mouse. — Cuenot, 1907.
It has been found in the laboratory as well as in the wild
state that mice may mutate (113, 136) to a yellow-bellied or
white-bellied condition (see Fig. 19), in which the ventral
hairs have an exceedingly long, light, apical band, in some
cases even to the exclusion of all other pigment. There is a
characteristically sharp demarcation on the sides and under
the chin, with a patch of darkly pigmented hair upon the
neck, shaped like a bow tie.
This bodily distribution pattern behaves as a dominant
to all known color characters or their combinations, includ-
ing yellow, i.e. it may be associated with the general coat
coloration of any other type. It has been found in agouti
(23, 137) and non-agouti forms (lJf.6), but not in combina-
tion with the lethal-yellow mutation. The wild gray mouse
possessing this character has a normal back and a white or
buff belly often tinged with red-brown along the sides (Aw).
UNIT-CHARACTERS (GENE MUTATIONS) 27
A black mouse bearing this pattern is known as black-and-tan
(a1) {51). The chocolate mouse with this pattern is a choco-
late-and-buff. The genetic relations of Aw to a1 are uncer-
tain, except that they behave as allelomorphs of each other
and of the agouti gene A.
When a gray mouse is crossed with a black-and-tan, the
offspring are light-bellied grays. Progeny of identical appear-
ance may be produced when white-bellied grays are crossed
with blacks. Black-and-tan and white-bellied gray have
usually been regarded as two additional allelomorphs of
the yellow, agouti, non-agouti series (51, 23). But it would
seem to be a more probable explanation that white belly
depends upon a gene closely linked with the agouti gene.
This explanation eliminates the paradox of the black-and-
tan, which, when crossed to gray, produces offspring in
which the back behaves as a recessive and the belly as a
dominant.
Brown (b)
The first definite record of the brown mouse is found in a specimen list
of mammals in the British Museum by Gray, 1843.
The brown condition (see Fig. 26) is one in which black
pigment throughout the coat, skin, and eyes is replaced by
chocolate (54, 110). This is thought to be due to an early
interruption of the reaction which regularly produces black
pigment. The mouse which would otherwise be wild gray
coated becomes a cinnamon when homozygous for the
brown gene, and the unticked or non-agouti form becomes
pure chocolate in color.
Blue dilution (d)
Blues may be thrown by blacks and then breed true. — Bateson, 1903.
A gray mouse homozygous for blue dilution (9) has a coat
exhibiting a washed-out appearance known as blue-gray
(53, 51f,, 72, 110). A non-agouti black when homozygous
for blue dilution (see Fig. 24) becomes lead colored like a
Maltese cat. A chocolate mouse which is also dilute is of a
28 LABORATORY MOUSE
''silver-fawn" color. The blue-dilute condition consists in a
reduction in number of pigment granules in addition to a
clumping of these granules. There is no noticeable change
in iris pigmentation, but the cleared retina is lighter in color
than that of the normal black eye.
Naked (N) (dominant hairless, "half-naked")
The whole bodies of these three little creatures were completely naked,
as destitute of hair and as fair as a child's cheek. There was nothing
peculiar about the snout, whiskers, ears, lower half of the legs and tail:
all of which had hair of the usual length and colour. — Gordon, 1850.
Naked (see Fig. 28) is a peculiar physiological condition of
the skin causing alternate waves of falling hair and regenera-
tion (66). These waves (108) pass from head to tail, three
or four waves being visible at a given time. Vibrissa? are
present as well as the short hairs upon the tail. The
homozygous naked (see Fig. 30) is devoid of tail hair and
vibrissa?, and is semi-lethal. Animals of this constitution are
difficult to raise and are usually sterile. These mice have the
skin normal in texture and general appearance. The genetics
of this variation as a dominant unit-character was first
worked out by Lebedinsky and Dauvart (1927).
Recessive hairless (hr) (rhinocerus?) (151, 3, 14)
In November, 1924, I received from a gentleman in North London, a
pair of pink, smooth-skinned, hairless mice, which he had captured in his
aviary. — Brooke, 19L26.
This type of hairless animal (see Fig. 29) has no tail hair
but retains vibrissa? (12, 130, 60). It has wrinkled, dry skin
of at least three times normal thickness. A few aberrant
hairs coil about within and even under the skin. Such hairs
may be seen in the dried skin, which is rendered transparent
by the natural oil contained within it. The skin is filled with
granular cysts. Hairless females are usually sterile and the
stock is maintained by breeding hairless males to their heter-
ozygous sisters. The gene for hairless (hr) is linked with
piebald (s).
UNIT-CHARACTERS (GENE MUTATIONS) 29
Short ears (se)
The mutation was found in a stock which originally came from the
Lathrop mouse farm and consists in a noticeable difference in size of ears.
— Lynch, 1921.
As the name would indicate, this variety is characterized
by small ears (see Fig. 27). It is due to arrested development
of the auditory pinna {127). When both short-eared and
normal-eared animals are found in the same litter, one is
often able to distinguish the classes upon the fourteenth day
after birth.
While the normal ear increases in length of pinna (87)
during the time from the fourteenth to the twenty-eighth
day from 0.71 to 1.16 cm. (63 per cent increase), the short
ear shows a gain from .60 to .76 cm. (27 per cent increase).
The skull shape of the short-eared mouse differs from that of
normals in that the nose is broader, while the cranium is
much narrower. The zygomatic arch is squarer than in the
normal. There is a certain amount of sterility noticeable
among short-ear animals. The gene underlying the develop-
ment of short ears is tightly linked with that for blue dilu-
tion and there is a relationship, not completely worked out,
between short ears and wavy tail. This latter relationship
will be touched upon under the heading of wavy tail.
Wavy tail
The behavior of this mutation is, like tailless, eccentric. — Gates, 1927.
Some mice from birth show in the tail a series of zigzag
waves (61) bent in the horizontal plane. Such a condition is
commonly found in short-ear stocks. Wavy tail is purely
a neuromuscular condition (87), more extreme when the
animal is excited and disappearing in sickness, death, or
under anaesthesia. The loci of the flexures are constant
throughout life, as may be shown by tattooing a spot at the
point of each flexure. X-ray photographs reveal that the
caudal vertebrae are unaffected. The extended wavy tail is of
normal length. Snell maintains (159) that wavy tail is but a
second expression of the short-ear gene. Yet in some short-
30 LABORATORY MOUSE
ear families wavy tail appears to be absent. In some long-ear
stocks it is present. In the absence of complete genetic
analysis it is impossible to say whether the short-ear stocks
with straight tails lack the wavy tail through absence of a
gene or merely through lack of muscle tonus. If the wavy
tail is not another expression of the short-ear gene, then it
is linked with short ears as the researches of Gates and Keeler
have shown. The inheritance is probably that of a weakly
dominant unit-character.
Flexed tail (/) (kinky?)
In all cases the tail is permanently rigid over a varying portion of its
length, this stiffness being particularly conspicuous proximally. The
rigidity may be accompanied by permanent V-shaped, U-shaped, spiral,
etc., flexures. ... — Hunt and Permar, 1928.
In some of the short-ear stocks bearing wavy tail a com-
plete right-angle flexure is found (11, 78, I4.8, 44)- The joint
is solidified by the fusion of vertebrae and the presence of an
osteosis. Sometimes two or three of these flexures may be
present in the same tail. This character may or may not
be that reported by Plate, 1910. Such heritable flexures are
found in long-ear stocks, but the identity or relationship of
these characters is uncertain. The inheritance of flexures has
been described by Hunt and Permar as a recessive which
sometimes fails to come to recognizable expression.
Danforth, {27), in speaking of kinky tail (see Fig. 34) says:
In these the caudal intestine instead of completely degenerating after
the sixteenth day as in normal individuals, persists until birth as small
remnants which become cystic or granular. Above these cysts the develop-
ing cartilages are thrown out of alignment and finally ankylose with each
other, forming permanent kinks.
Posterior reduplication
By selection there has been developed a strain of mice which give a
high percentage of young showing varying degrees of posterior reduplica-
tion. — Danforth, 1930.
This character (see Fig. 32) ranges from Polydactyly to
completely formed additional posterior parts including legs,
genitalia, and alimentary tract {27). The inheritance of
the character is recessive and approximates the behavior
UNIT-CHARACTERS (GENE MUTATIONS) 31
expected of a unit-character, with a deficiency probably
due to its low viability.
Waltzing (v)
In 80 b.c. "in the ninth moon, a yellow mouse was found dancing with
its tail in its mouth in the gateway of the palace of the Kingdom of Yen
[now the province of Chili]. The animal danced incessantly. The king
asked the queen to feed it with wine and meat but this did not interfere
with the performance. The mouse died during the night. — Annals of the
Han Dynasty (translation by Quentin Pan).
Waltzing mice (see Fig. 22) are unable to orient themselves
upon a horizontal plane, and this results in a rapid and erratic
turning or whirling. Waltzers make many turning, twist-
ing, and jerking head movements {183). Waltzers are totally
deaf {182). Different investigators disagree as to whether
or not the semicircular canals are morphologically normal.
Waltzers are very delicate, poor mothers, and quite suscep-
tible to cold. The most common inbred strain of Japanese
waltzers in America is non-agouti black and bears a high
grade of recessive piebald, with the anatomical characteristics
of Mus bactrianus (wagneri). Waltzing is inherited as a sim-
ple recessive (25, 31, 32, 61, 76).
Gates (63) bred a waltzer containing but one dose of
waltzing, which presumably through a faulty cell division
had lost that portion of the normal chromosome which
contains the allelomorph of waltzing. Painter's histological
investigation (142) confirmed this conclusion.
Shaker (sh)
The mutation shows itself principally in the form of nervous head
movements. — Lord and Gates, 1928.
The shaker (126) makes choreic head movements similar
to those of the waltzer but lacks the circling movements.
The character is recessive and linked with albinism and pink-
eyed dilution.
Rodless retina (r)
Microscopic sections of these eyes showed the total absence of visual
cells (rods). — Keeler, 1924.
32 LABORATORY MOUSE
This retinal defect (see Fig. 36) is characterized by com-
plete absence of rod and external molecular layers and a
great reduction of the cell number in the external nuclear
layer (86, 90). The condition is readily detected by examin-
ing histological sections of the retina. The iris of the rod-
less eye contracts (88, 89) upon exposure to light and the
blindness of rodless mice may be detected only by precise
and carefully conducted animal-behavior tests (87). Rod-
less eyes secrete no visual purple (90) and produce no elec-
tric action current responses (99) to stimulation by light.
The recessive gene producing rodless retina is linked (98)
with that producing silver.
Dwarf (dtv)
In the case of dwarf mice, mature individuals are only about one-fourth
the weight of their normal brothers and sisters, scarcely bigger, in fact,
than the ordinary mouse 16 or 17 days old. — Snell, 1929.
These creatures (see Fig. 33) are probably pituitary-
deficient dwarfs.1 The character is determined by a reces-
sive gene (160).
Hyperglycemia (hy)
The findings obtained with the second generation confirmed the con-
clusion that hyperglycemia, like albinism, is a recessive character. —
Cammidge and Howard, 1926.
It has been definitely established (13) that a certain strain
of mice bear a gene, which in the homozygous state raises
the fasting blood-sugar proportions. Whereas normal mice
have a blood-sugar content of 74-84 mg. per 100 cc. of blood,
the mutant strain bears from 113-124 mg. per 100 cc. The
factor concerned is not linked with albinism but further
genetic analysis is wanting.
Other characters. Numerous other mouse variations are
known to breeders of mice. Some of these characters are
1 A paper by P. E Smith and E. C. MacDowell in the Anatomical Record, vol.
46, p. 249, published too late for inclusion in the bibliography, confirms that the
dwarfed condition is due to anterior pituitary deficiency and may be corrected by
injection of rat pituitary.
UNIT-CHARACTERS (GENE MUTATIONS) 33
erratic in their appearance and may depend upon several
factors, genetic or environmental. Hagedoorn reported a
genetic modifier of blue dilution (72). Heterozygosity for
brown, pink-eye dilution, or albinism also has a tendency
to lighten the coat. Little and Tyzzer {122) believe that
susceptibility to development of a certain sarcoma found in
the Japanese waltzing mouse is dependent upon three or four
independently inherited Mendelizing factors. The evidence
is derived from a cross between Japanese waltzing mice and
ordinary fancy mice in which the first generation was suscep-
tible but in the second generation there appeared a certain
percentage of mice of non-susceptible constitution. Other
tumor susceptibilities (see Fig. 31) have been demonstrated
to be hereditary {121, J>3, 12k, 165).
Several times in recent years a black-silver strain of mice
has thrown occasional individuals bearing a symmetrical
lacing pattern of white hairs. Its genetics is complex. Con-
genital cataract and stationary pupils have been found to
run in certain mouse families. A dilution effective in com-
bination with pink-eyed black was found several years ago,
but has not been completely analyzed. Recently a separa-
tion of the metopic suture, parted frontals (see Fig. 35), was
reported (97) as a dominant unit-character. A twisted con-
dition of the nasal bones behaving irregularly in heredity
was also found (96).
Another strain of mice produces individuals lacking kid-
neys (6), or having lesions of the eyes, head, or feet (120).
These are probably related, or expressions of the same
process determined by the same genetic factors.
Nomenclature. The compound breeds of the house mouse
are merely combinations of the simple characters already
described. It is customary in scientific circles to designate
the breeds by analytical names, but the fancier and layman
often employ other terms, usually descriptive. In the follow-
ing list are given the more common fancier's terms and their
analytical equivalents followed by their genetic formulae
in terms of mutated genes.
34
LABORATORY MOUSE
Fancier's Term
Scientific Term
Genetic Formula
Gray
Gray agouti, wild
No mutations
Black
Non-agouti
a a
Cinnamon
Brown agouti
bb
Chocolate
Non-agouti brown
aa bb
Fawn with pink eyes
Pink-eye agouti
PP
Clear fawn with pink eyes
Pink-eye brown agouti
bb pp
Lilac, blue-lilac
Pink-eye non-agouti
pp a a
Champagne, cafe au lait
Pink-eye non-agouti brown
pp a a bb
Blue, maltese
Dilute non-agouti
dd a a
Silver-fawn
Dilute non-agouti brown
dd aa bb
Pearl
Pink-eye dilute non-agouti
pp dd aa
Silver-champagne
Pink-eye dilute brown non-
agouti
pp dd bb aa
Yellow
Yellow, lethal yellow
AYA
Sooty, sable
Sooty, sable (one of the ex-
pressions of lethal yellow
often carrying non-agouti)
AYa
Cream, light yellow
Dilute yellow
dd AYA
Pied, piebald, Dutch spotted
Recessive spotting
ss
Variegated
Dominant spotting
Ww
Black-eyed white
Black-eyed white
Ww ss
Black-and-tan
Yellow-belly non-agouti
aa1, atat
Blue-and-buff
YTellow-belly non-agouti di-
lute
dd aa1, dd alaf
Chocolate-and-buff or
Yellow-belly non-agouti
bb aa1, bb alal
Brown-and-tan
brown
Yellow-belly gray
Yellow-belly agouti
Aw A,AWa or .4 a'
Tricolor
May refer to several com-
binations, the most com-
mon of which is probably
yellow-belly non-agouti
spotted
alal ss, a1 a ss
Mexican
Recessive hairless
hr hr
Japanese waltzer
Usually non-agouti piebald
waltzer
aa ss vv
Short ears
Short ears
se se
Some of the more common fancy varieties of mice are
figured in color by Schuster (157) and Little (110).
NORMAL INHERITANCE
Indeed they (white mice) always bring forth white ones.
— Pallas, 1766.
For many years it has been known that when white mice
are crossed with pure-bred grays, the immediate offspring
will be gray and in the second generation albinos will reap-
pear (36). The true nature of this transmission, however, was
first clearly understood in 1900, when Mendel's Law was
rediscovered.1
Work since that time has shown that the majority of
house-mouse characters are inherited in the same simple
fashion as albinism. Most of the fancy characters are reces-
sive like albinism, which, when crossed with the wild gray
type, produces all grays in the first generation and one
recessive out of four in the second generation.
The mechanics of such inheritance is clearly known. The
physical determiners underlying these hereditary variations
are located in the minute rod-shaped bodies (chromosomes)
within the nucleus of each cell of the body- In all mouse
body-cells there are twenty kinds of these chromosomes
(see Fig. 9) and two of each kind, one of each pair having
been received from the father and one from the mother.
These chromosomes are reduced from the diploid (double)
number to the haploid (single) number at the formation of
the gametes (eggs and sperm), so that each gamete contains
only one of each pair. When two gametes unite (an egg with
1 litis, 1924 (.SO), p. 68, says: "We have already heard from Fr. Hornish and
Inspector Nowotny that Mendel raised mice in one of his two rooms, and not only
white ones but also grays, and crossed them with each other. It is very possible that
through these more dramatic researches the revelation of dominance and segrega-
tion appeared to him for the first time. Indeed, he mentions nothing about it.
This is not to be wondered at because industry in natural science at once made an
ecclesiast suspicious in the eyes of many clerical zealots, to whom the undertaking
of animal breeding appeared highly immoral."
36
LABORATORY MOUSE
a sperm) to form an embryo, the double number is again
restored.
A pure-bred gray-coated mouse receives a determiner for
pigment development (C) from its father and one from its
mother. When its gametes are formed, each will contain
a single pigment determiner. Hence, in matings with
another pure-bred gray, a pair of pigment determiners will
enter into each embryo and nothing but pure-bred pigmented
young will be produced.
In like fashion an albino receives one determiner for
albinism (c) from its father and another from its mother, and
Fig. 6. Diagram illustrating the inheritance of a simple, recessive, mendelizing unit-character
such as albinism. Black wafer = C gene, white wafer = c gene.
produces gametes each bearing a determiner for albinism.
Thus, when two albinos are mated together their offspring
will receive a determiner for albinism from each parent and
hence all are albinos.
If an albino is mated with a pure-bred gray, the albino
will contribute an albino determiner (c) and the gray will
contribute a pigment determiner (C) (see Fig. 6). It so hap-
pens that the pigment determiner in this case completely
dominates over the albino determiner and the cross-bred
offspring are pigmented, giving no evidence that they carry
an albino determiner. A cross-bred gray carrying albinism
produces two kinds of germ cells in equal numbers, half
NORMAL INHERITANCE 37
containing the pigment determiner and half containing the
albino determiner. Now if two cross-bred grays, each carry-
ing an albino determiner, be mated, the two kinds of germ
cells (C and c) will come together purely at random and the
offspring will appear in the proportions of 1 pure-bred pig-
mented: 2 cross-bred pigmented: 1 pure-bred albino. The
visible classes will be 3 pigmented (containing C) : 1 albino.
Gametes of father
C c
Gametes
of mother
CC
Cc
Cc
Combinations among
the offspring
An actual experiment of this sort (combined data from Little
{110) and Keeler {87)), produced 2994 pigmented young and
1029 albinos or a ratio of 2.91 to 1, the theoretical expecta-
tion being 3017.75 pigmented: 1005.75 albinos.
Some of the mouse genes have more than two alternative
forms or different chemical states. The color gene {€) has
at least four such allelomorphs in mice. These are (1) normal
pigmentation (C), (2) chinchilla {cch), (3) extreme dilution
or Himalayan albinism {cH), (4) complete albinism (c).
Each member of the series dominates in crosses over those
which follow it in the same series. That is, when an animal
bears heredity for any two of these characters, the one
appearing first in the list will be expressed in the coat. For
example, if a chinchilla be crossed with an albino, the first
generation will be chinchillas and the second generation will
contain an average of 3 chinchillas to 1 albino. No more
than two members of such a factor series may exist in a
single individual (one in each of the two chomosomes making
up a particular pair).
If a normally pigmented animal carrying a chinchilla
factor be crossed with an extreme-dilute animal carrying
albinism, the first generation will consist of equal numbers of
normally pigmented animals and of chinchillas. Half each of
38
LABORATORY MOUSE
the normals and of the chinchillas will carry extreme dilution
and half will carry albinism.
Gametes
Gametes
C cH
normally pigmented
cch QH
chinchilla
C c
normally pigmented
cch c
chinchilla
Zygotes
If these hybrid-generation animals be mated at random
four kinds of germ cells will be formed in equal numbers and
will unite also at random, producing on the average 7 normals,
5 chinchillas, 3 extreme dilutes, and 1 albino. Of the 7 nor-
mals, 1 will be pure bred, 2 will carry chinchilla, 2 will carry
extreme dilution, and 2 will carry albinism. Of the 5 chin-
chillas, 1 will be pure bred, 2 will carry extreme dilution, and
2 will carry albinism. Of the 3 extreme dilutes, 1 will be
pure bred, and 2 will carry albinism. The 1 albino will be
pure bred. See diagram.
Gametes
C cch cH c
Gametes
c
CC Ccch
normal pigment normal pigment
CcH Cc
normal pigment normal pigment
ch
cchc cch cch
normal pigment chinchilla
cch CH
chinchilla
cchc
chinchilla
H
cHC
normal pigment
CH cch
chinchilla
CH CH CH c
extreme dilute extreme dilute
c
cC
normal pigment
c cch
chinchilla
cP c cc
extreme dilute albino
Suppose we have a mouse bearing two independent unit-
characteristics (borne in different chromosomes), for ex-
ample, rodless and albinism. The determiner for the albino
character lies in one chromosome pair and that for rodless
in an entirely different pair. The genetic formula of this
NORMAL INHERITANCE
39
mouse with respect to the two characters named will be
rrcc, while that for a normal-eyed pigmented mouse will be
RRCC. The gene for rodless is represented by r, the gene
for normal eye by R; the gene for albinism by c, the gene for
colored coat by C.
If we cross a rodless albino with a normal-eyed pigmented
mouse all the immediate offspring will be Rr Cc. The gene
for normal eye dominates over the gene for rodless and thus
the offspring are normal eyed. The pigment-forming gene
dominates over the albino gene and thus the offspring are
pigmented. Yet they carry (recessive) heredity for both rod-
less and albinism.
These normal-appearing offspring, carrying as recessive
genes albinism and rodless, form four kinds of gametes in
equal numbers, RC, Re, rC, and re. If two such double
heterozygotes be mated together they will produce offspring
in the proportion of 9 normal-eyed pigmented, 3 normal-
eyed albinos, 3 rodless pigmented, and 1 rodless albino.
The checkerboard below shows how these combinations
could arise through the random union (48) of these four types
of gametes.
RC
Gametes
Re rC
Gametes
RC
Re
rC
RC
RC
Re
RC
rC
RC
re
RC
RC
Re
Re
Re
rC
Re
re
Re
RC
rC
Re
rC
rC
rC
re
rC
RC
re
Re
re
rC
re
re
re
Zygotes
An experiment (87) of this kind yielded 165 normal-eyed
pigmented, 64 normal-eyed albinos, 51 rodless pigmented,
and 29 rodless albinos, or a ratio of 8.5 : 3.3: 2.6: 1.5.
40
LABORATORY MOUSE
Normal-eyed
pigmented
Normal-eyed
albinos
Rodless
pigmented
Rodless
albinos
Found
165
64
51
29
Expected
173.7
57.9
57.9
19.3
If the double heterozygotes be mated back to the parent
pure for the two recessive characteristics, four classes of
offspring will be expected in equal numbers, namely, normal-
eyed pigmented, normal-eyed albino, rodless pigmented, rod-
less albino. This test (87) yielded of those classes respectively
66: 54: 68: 51 or ratios of 1.1: .99: 1.1: .93.
Gametes of double heterozygotes
RC Re rC
Gametes of re
double
Found
Expected
RC
re
Normal-
eyed
pigmented
Re
re
Normal-
eyed
pigmented
rC
re
Rodless
pigmented
re
re
Rodless
albino
66
54
68
51
59.7
59.7
59.7
59.7
The gene for two or more unit characters may lie at differ-
ent points or "loci" upon the same chromosome, a relation-
ship known as linkage. Linkage is measured by the amount
of crossing-over, or recombination. Ordinarily in the forma-
tion of gametes the two chromosomes of an homologous
pair, which have lain side by side in immature germ cells,
separate at maturation and one passes to each daughter cell.
Each functional gamete (egg or sperm) thus contains one
representative (not two) of each gene. The chances are even
that it will be the representative derived from the father or
that derived from the mother.
Occasionally chromosomes break (see Fig. 7) transversely
while lying elongated in pairs previous to the reduction
division. When the break is repaired the broken ends may
become united differently from before. The chromosomes
which originally bore RC and re respectively may after a
NORMAL INHERITANCE
41
"crossing-over", bear Re and rC. The percentage of cases
(times in a hundred) in which crossing-over occurs is called
the crossover percentage. The nearer together two genes
lie in the same chromosome, the fewer chances there are for
breaks to occur between them resulting in recombination
or crossing-over. Hence the percentage of crossing-over is
taken as a measure of the nearness together of genes or of
the linkage strength (16) between them.
In cases where linkage is involved, new combinations
(recombinations) of two characters may be difficult to obtain.
Fig. 7. Diagram of a pair of chromosomes showing the linkage relationship of two
pairs of genes before, during, and after a crossing-over.
Suppose we select a mouse bearing two genes located in the
same chromosome, for example rodless and silver (rrss).
Should we cross this rodless-silver to a normal-eyed unsil-
vered mouse (RSRS) the offspring will be rsRS and will be
normal-eyed unsilvered. When these animals form gametes,
r and s being in the same physical chromosome will behave
ordinarily as units as also will R and S for a like reason.
Hence there will be ordinarily two, and only two, kinds of
gametes, namely, rs and RS. If two such animals are mated
together they will produce ordinarily but two types of
offspring: normal-eyed unsilvered (RSRS or RSrs) and rod-
less silver (rsrs). But when there is a crossover, two other
types of gametes are produced (rS and Rs), making possible
the occurrence of occasional rodless unsilvered animals (rSrS
or rsrS) and normal-eyed silvers (RsRs and rsRs). We may
detect the percentage of crossovers between r and s by
crossing an rsRS animal to an rsrs (see Fig. 8).
42
LABORATORY MOUSE
Gametes of rsRS parent
RS Rs rS
Gametes
of
rrss
parent
RS
Rs
rS
rs
rs
rs
rs
rs
Normal-
Normal-
Rodless
Rodless
eyed
eyed
unsilvered
silver
unsilvered
silver
Crossover classes
If the characters silver and rodless were not linked, we
should expect equal numbers of all four classes. If they are
linked, we expect the second and third classes to be small in
comparison with the first and fourth. The second and third
Fig. 8. Diagram of a back-cross illustrating the linkage between rodless retina (r)
and silver pelade {x). Animals with unshaded eyes are rodless.
classes are produced only from gametes in the genesis of
which a crossover has occurred between silver and rodless.
A back-cross of the kind described (98) gave 9 unsilvered
normals, 1 unsilvered rodless, 1 silver normal, and 5 silver
rodless. More extensive breeding tests indicate that a cross-
over takes place between silver and rodless at the formation
of about 12 per cent of the gametes.
If three determiners are located at different points in the
same chromosome, as are albinism (172), shaker (126), and
pink-eye dilution (172), we may determine their relative posi-
tions by the percentage of crossovers obtained in breeding ex-
periments. If a crossover occurs between albinism and shaker
3 times out of a hundred and between shaker and pink-eye
dilution 15 times out of a hundred and between albinism and
NORMAL INHERITANCE
43
pink-eye dilution 18 times out of a hundred, then the three
genes must lie in the order: albino, shaker, and pink-eye
dilution. The indicated distance between albino and shaker
is about one-sixth that between albino and pink-eye dilution.
In Fig. 9 a number of determiners (genes) for mouse
unit-characters are represented as located upon diagram-
matic chromosomes of the mouse, to illustrate the genetic
n
VJ
r\
u
naked
U
r\
n
agouti I
white -
belly
u u
Olwailzer
0 o
Fig. 9. Diagram of chromosomes of the house mouse (22) with genes for unit
characters distributed arbitrarily among them to show genetic independence or
linkage of the characters.
independence or linkage found experimentally to exist be-
tween these determiners.
Besides the two linkage systems already mentioned {172),
linkage has been shown to exist between recessive spotting
and recessive hairless (161), and between short ears and
dilution (64-, 159). It is possible, as already suggested, that
agouti and white-belly may also be linked characters, rather
than allelomorphs.
According to present data, known hereditary characters
have their determining genes located in 9 of the 20 pairs of
chromosomes of the house mouse. It is reasonable to sup-
pose that some day characters will be found in the remaining
11 pairs as well as other genes within those chromosomes
already bearing determiners for fancy variations.
VI
ABNORMAL INHERITANCE
The characters non-agouti, pink-eye dilution, blue dilution,
brown, recessive spotting, waltzer, rodless, shaker, and the
albino series of allelomorphs seem to be recessive unit-
characters and to behave according to the rule for simple
Mendelian inheritance. Varieties characterized by these all
breed true because they are homozygous. Yellow-belly
behaves as a dominant unit-character and breeds true only
when homozygous. Yellow and dominant spotting do not
breed true but produce only 50 per cent of offspring possess-
ing the characters in question, because they are dominant
lethals and so cannot be made homozygous.
Normal Overlaps. Silver behaves as a recessive unit-
character but seemingly does not always breed true because
some silvered animals are with difficulty recognized as such.
Silvered mice throw a certain percentage of animals of such a
low grade of silver that they may not be distinguished read-
ily from non-silvered animals, although they are genetically
silvers. Such animals which are genetically of a mutant type
but somatically are capable of classification as of the normal
type are known as normal overlaps.
Dominant Lethals. Two of the unit-characters of mice,
namely yellow and dominant spotting, are dominant lethals.
By this we mean that animals bearing one factor for the
character exhibit the character, but that animals bearing
two factors for the character are non-viable. Thus, all yellow
mice carry a non-yellow factor as a recessive. When two
yellows are mated together they produce on the average one
homozygous yellow which dies, two yellows heterozygous
like themselves, and one non-yellow animal, as was first
pointed out by Cuenot (££).
The same is true for dominant spotting. Two dominant-
spotted animals produce on an average one homozygous
44
ABNORMAL INHERITANCE
45
dominant-spotted animal which dies of anaemia (115), two
dominant spotted (heterozygotes), and one non-dominant-
spotted animal. Strains of dominant spotting exist which
throw self animals as recessives. (See Fig. 21.) These are
the non-dominant-spotted class. Other strains, known as
black-eyed whites, are homozygous for recessive spotting
and consequently produce piebald animals instead of selfs,
as the non-dominant-spotted class.
Hereditary Sterility. Dominant hairless (naked) individ-
uals which are heterozygous are often produced, but are
usually sterile. In one case a homozygous naked female pro-
duced young but had no milk to nurse them. Possibly the
mutation which affected the hair follicles also disturbed the
Gametes
N
N
NN
Homozygous naked
(sterile)
Nn
Heterozygous naked
Nn
Heterozygous naked
nn
Normal
Gametes
processes of mammary development or secretion. Dominant
hairless stocks are maintained by mating heterozygous indi-
viduals with each other or by mating heterozygotes to
normals. In both types of cross one half the progeny are
wasters, that is, are not of the desired type, heterozygous
naked.
Gametes
N
Gametes
Nn
Heterozygous naked
Nn
Heterozygous naked
nn
Normal
nn
Normal
Recessive hairless usually produces sterile females and
fertile males and hence the strain is readily preserved by
46 LABORATORY MOUSE
mating hairless males to heterozygous females. The resulting
hairless males are crossed to their heterozygous sisters, and
so on.
A certain amount of sterility is encountered in short-eared
mice. This may or may not be associated in some fashion with
the short-ear character, but is complicated in its inheritance.
The sterility often found among waltzers is usually due to
the fact that these animals are very delicate and require the
best of care in a very special environment. Under ideal con-
ditions they breed well. They are, however, poor mothers
and their young should when possible be given to a foster
mother of some non-waltzing variety to nurse.
VII
THE BREEDING OF MICE IN LABORATORIES
Mating Habits. The oestrous cycle (2) of the mouse lasts
from three to four days. In only a few hours within this
cycle will the female permit the amours of a male; at other
times she avoids his attentions by slipping quietly into the
nest or by climbing up the side of the cage.
During the receptive period her reactions to courtship
change completely. When her suitor approaches, she often
rears upon her haunches, throws her paws up in a defensive
attitude, closes her eyes, and gives a characteristic short
squeak. The male nervously licks her face, sniffs at her
genitals, and attempts to mount. The female often runs
away into the nest or up the side of her cage only to return to
the former trysting place. There are numerous unsuccessful
attempts at copulation before the completed act takes place.
The secretions of the male form a soft vaginal plug which
quickly hardens, cementing the vagina shut and thus pre-
venting escape of the sperm until after fertilization (125) of
the eggs is accomplished. The vaginal plug is usually lost
within twenty-four hours.
Uterine Development (129, 81). The sperm ascend the geni-
tal tracts within a few hours after copulation and fertilize
the eggs as they are shed from the follicles before they enter
the uterus. The fertilized eggs descend into the uterus where
they implant about the fifth day. At this time development
has progressed to about the primitive streak stage. About
the eighth day, at a stage corresponding to that of the three-
day chick, all the foetal organs are laid down. The cerebral
ganglia are growing out, and the limb buds are forming,
while the heart has long been pumping blood through the
foetal arches. The retina has invaginated and the lens is
formed.
47
48 LABORATORY MOUSE
The young are born usually between the nineteenth and
twenty-first days after mating {103, 29). In Japan wild
house mice and those of the fancy are often termed "twenty-
one-day mice" on account of the length of the gestation
period.
Birth. Just prior to parturition the female may be ob-
served to become restless. During this period she may con-
struct an elaborate nest by winding strands of nesting tissue
to form a ball, tucking in loose ends here and there.
At the birth of young, the reactions of the mother seem
to vary greatly with such factors as her natural temperament,
health, company, and the degree of seclusion provided by her
cage. Some mice retire to the nest for parturition while
others continue their routine reactions about the cage.
Reaction to the new-born young may vary from almost
completely ignoring them where they happen to drop out-
side the nest, to birth within the nest followed by careful
washing and cuddling.
Four or five minutes of uterine contraction may be re-
quired to give birth to a mouseling, followed within a minute
by the expulsion of the placenta and perhaps portions of
the fcetal membranes. The female chews and occasionally
devours the placenta.
The new-born mouse is a naked little creature about two
and a half centimeters long with well proportioned head,
body, and feet. It is unpigmented save for the dark ring of
the iris, which is visible through the translucent eyelids. The
ears are folded forward and sealed.
The new-born mouse left to itself may remain motionless
for as long as a minute before it gives its first tiny gasp,
followed by another and another. These gasps are con-
tinued at irregular intervals, often accompanied by violent
contractions of the body and especially the breathing
muscles. Within five minutes the mouseling is breathing
regularly and lying quietly except perhaps for an occasional
twitch of a leg or a sucking movement of the mouth.
Nursing takes place as soon as the mother huddles over
THE BREEDING OF MICE IN LABORATORIES 49
the young mouse subsequent to its metamorphosis into an
air-breathing creature, at times perhaps even before it is dry.
The first period of nursing may continue as long as fifteen
hours, if the mother is not interrupted.
Under poor conditions some mice will not nurse their
young. In case a mouse refuses to nurse young of great
value to the investigator, they should be fostered. If young
mice have nursed it is evident, because milk contained in the
stomach shows through the left side as a cream-colored
crescent.
Growth. As with most helpless infants, during the first
period of their lives, the reactions of young mice are con-
fined chiefly to nursing and sleeping, while their bodies grow
rapidly in size and differentiation progresses in the more
retarded organs such as those of special sense. The rods of
the retina, for example, are developed after the fifth day.
The pigmented hair within the skin is faintly visible upon
the second or third day and is well developed by the eighth
day, when the skin becomes scaly, probably due to a shedding
of the external surface as dandruff. By this time the little
mice move blindly about the nest and even venture into the
world outside, only to be hustled back in the mouth of their
mother, who continually washes, feeds, and looks after them.
By the thirteenth day the truancy of these little balls of
fur, still unsteady upon their feet, becomes too great for their
attentive mother, who still repeatedly carries them back to
the nest. They occasionally escape to a sequestered corner
of the cage, where they test things with their paws, noses,
tongues, and vibrissa?. They sit and wash their faces, nibble
morsels of food, and blink at the light with their newly
opened eyes.
In the childhood of the mouse there has been observed no
period of play such as young rats enjoy when they mouth,
kick, tussle, clutch, and roll with each other. However, be-
tween the fifteenth and twenty -fifth days young mice unused
to handling are more restless and more active than usual,
squeaking, scampering, leaping, and seeking to hide them-
50 LABORATORY MOUSE
selves at the slightest noise or motion. The degree of this
activity also has a genetic basis, because members of certain
strains are much more active than members of other strains.
By the thirteenth day the young mouse is almost an adult
save in size and sex differentiation. Sex maturity is usually
reached between the second and third months, although
mice increase a small amount in size during the several
succeeding months.
Fostering. Fostering is often desirable where the female
is of a feeble strain, is a poor mother, or is one from which
a maximum number of offspring is desired.
In fostering it is a good practice to employ as nurses
females which are first-generation offspring of a cross between
two inbred varieties which show great vigor, although any
docile vigorous female will do. A number of these prospective
nurse mothers are mated simultaneously with those whose
young are to be fostered so that nurses will be available
when the desirable young are born.
Some foster mothers object to an exchange of young, espe-
cially if the mice to be fostered are younger than her own
litter. The foster litter and the foster mother's own litter
are shaken together gently by some investigators in order
that the foster mice may obtain the odor of the foster moth-
er's nest and be more acceptable. The mice to be fostered
are picked out and given to the foster mother, while the
foster mother's own litter are killed.
If a female mouse has not nursed much, she will usually
breed within twenty-four hours after parturition.
Killing. Some investigators prefer to drop all discard mice
into a covered jar containing a piece of cotton saturated with
ether, although simple mechanical methods of terminating
their existence are both adequate and painless.
Parasites. Even with the best of care a mouse colony may
occasionally be infested with fleas, mites, or lice to the ex-
tent that they prevent breeding, although these parasites
seldom prove fatal. Pyrethrum powder or pulverized tobacco
dusted upon the animals from time to time are good preven-
THE BREEDING OF MICE IN LABORATORIES 51
tive measures. However, should the infestation persist, the
mice may be individually caught by the tail, dipped in a
warm, very dilute solution of stock-dip, and allowed to dry
in a warm place. If metal cages are employed, the nest and
food may be removed and the whole cage dipped, mice and
all. We have found Parke Davis and Company's Kreso-Dip
satisfactory for this purpose.
Mice are occasionally attacked by a white fungus which
grows upon their ears. It is difficult to eradicate and hence
if the affected animal may be spared it should be killed. If
the fungus affects only the tip of an ear when discovered, it
may frequently be eliminated by clipping off the ear below
the affected region. Adult mouse ears seldom bleed when
snapped off, but if they should, a little sodium subsulphate
powder will quickly stop the flow.
Mice sometimes harbor a tapeworm for which the cat
serves as definitive host. Accordingly, it is advisable to
exclude all cats from the mouse room. There are other more
obvious reasons why cats are undesirable tenants of a
murarium.
Diseases. Some strains of fancy mice are affected with
hereditary tumors. Those involving the mamma? of the
female are the most common. If a tumorous female is very
valuable, occasionally a single litter of mice may be pro-
cured from her after surgical removal of the growth. As a
general practice animals bearing tumors should be discarded
as the results seldom justify the efforts to save them.
Mice are susceptible to a number of non-specific organism-
borne diseases {171, 133), such as surra {Trypanosoma evansi),
apoplectic septicemia, fakosis {Micrococcus caprinus), fowl
cholera {Bacterium cholerce gallinarum), trichosis {Trichinella
spiralis), the disease caused by Bacillus piliformis, sarcospiri-
diosis, botryomycosis, and coccidiosis. These diseases will
seldom be encountered in a well-kept mouse colony, and
hence a mere mention of them will suffice here.
By far the worst disease among laboratory mice is para-
typhoid {175) (often known as diarrhoea) caused by Bacillus
52 LABORATORY MOUSE
typhi murium. If one can possibly spare the mice, it is
advisable to kill off each day all sick animals and sterilize
the cages at once. Some adult mice are not killed outright
by the disease, but they remain carriers of the condition and
may do much damage by spreading it. This disease is
usually fatal to animals between fifteen and twenty-five days
of age. A few recover, and if these are females they may
be normal and reproduce, but if they are males they will
usually be sterile, due to the fact that the poisonous, diar-
rhoeic feces "scald" the scrotal region, causing the forma-
tion of scar tissue. The stiff scar tissue prevents the descent
of the testicles necessary for fertility. Thus it is advisable
in every case to kill all young affected males. If valuable
young females are preserved, they should not be kept in the
mouse room.
By the enumeration of the above pathological conditions
and insistence upon drastic measures to eliminate disease
from the mouse colony, it is not intended to give the im-
pression that mice are weak and susceptible to all sorts of
sickness, making them difficult to raise in quantity. There is
no limit to the number of healthy mice which may be main-
tained in a well-tended murarium. Five thousand is not an
unusual size of colony for an experimental laboratory.
Breeding Cages. There are a number of practicable de-
signs for successful breeding cages, but the most satisfactory
are those which provide adequately for certain requirements
peculiar to the mouse. The design of the cage should take
into consideration size convenient for handling, space oc-
cupied, dry feed, closed water bottles, changeable nesting
material, absorption of urine, and ease of sterilization. A
mouse cage meeting these requirements has been developed
at the Bussey Institution (see Fig. 10).
The cage is made of galvanized-iron wire netting of
^ inch mesh. The dimensions of the cage are 12 inches long,
7 inches wide, and 7 inches high. It rests upon half an inch
of sawdust in a galvanized-iron pan 15 inches long, 13|
inches wide, and 3| inches deep. Two cages nest side by
THE BREEDING OF MICE IN LABORATORIES 53
side in each pan. These pans with the contained cages are
kept upon racks of dimensions to accommodate them.
The cage proper has a sloping front provided with a gal-
vanized-iron door which is held shut by gravity and the
weight of the water bottle. The iron door is convenient as a
memorandum space for numbers or notes not recorded in the
official register.
A dog biscuit is wired to the rear wall. The cage is pro-
vided with a handful of shredded tissue paper for nest ma-
Fig. 10. Wire mouse cage used at the Bussey Institution.
terial and with a feed dish. A numbered metal tag for cage
identification is wired to the sloping front, or the number
may be painted on the iron door.
Once a week the cages should be cleaned with a stiff brush,
provided with fresh nesting tissue, fresh sawdust, and clean
food dishes, and about once a month they should be washed.
Sanitary Precautions. Because mice are subject to several
infectious diseases, cages should be of a material which may
be readily sterilized. If cages are made of metal they may
be sterilized by immersion in boiling soapy water, brushing,
and then dipping in a solution of "Kreso" or other disinfec-
tant. Cages should be disinfected at least once a month
in absence of disease and oftener if the colony is infected.
Cages in which diseased animals have lived should be dis-
infected immediately.
Animals dying from no matter what cause should be
removed from cages at once, because the carcasses are often
partially eaten by other mice and disease may thus be spread.
54 LABORATORY MOUSE
Water. Water standing in an open dish in a mouse cage
becomes quickly contaminated with urine and feces and is
unfit for drinking. The greatest difficulty, however, is that
active mice will continually run through any open water
dish, very frequently splashing water upon their fur. Often
they become chilled and contract pneumonia, which usually
proves fatal.1
For these reasons a closed drinking-water supply is best.
A bottle fitted with a rubber cork pierced by a glass tube is
most satisfactory. The glass tubing should be drawn to a
nipple and the end smoothed in the flame, because water
will drip through a large opening. This provides constantly
a hanging drop which is licked by the mice when they
desire it.
Records. Every animal should be numbered and registered
with regard to individual number, sex, description, known
recessive characters, parents, date of birth, and often disposi-
tion and date.
A card index should be kept, bearing the numbers of the
cages upon the guide cards and a card filled out for each
animal with data on individual number, sex, purpose and
date of mating, and cage number. This should be filed at
the proper place within the index.
When a female becomes pregnant, she should be given a
separate cage, because, with other mice in the cage, some
mothers become excited and kill their young. New-born
mice are often killed by males or more often still by other
females in the cage. Date of birth, record number of the
father, and information concerning the young not yet reg-
istered may be jotted down upon the card of the mother.
Numbering. A satisfactory system of marking mice for
identification purposes is to punch the ears with a chick
punch. The following simple system of position marks is
used almost exclusively by American geneticists. The first
1 The practice of providing open water dishes may have occasioned the state-
ment of Aristotle concerning the white mice of Pontis that if they drink water
they will die.
THE BREEDING OF MICE IN LABORATORIES 55
three numerals, 1, 2, and 3, are denoted by holes in the ear
at top, side, and bottom respectively. The second three,
4, 5, and 6, are represented by notches in the edge of the
ear at top, side, and bottom. The next three numerals, 7, 8,
and 9, are indicated by combinations of two notches, 7 being
notches at both top and side, 8 being notches at both side and
bottom, and 9 being notches at both top and bottom.
With this system, employing the right ear for units and
the left ear for tens, one may number animals from 1 to 99.
One hundred has a hole in the center of each ear, but may be
distinguished from 200, 500, 700 etc., by age, color, parents,
cage number, and other records. By these data one may also
identify mice whose individual record numbers bear the
same last two digits.
Temperature. Mice are quite sensitive to changes in
temperature. A cold draft from a window may prove fatal
to a high percentage of a colony within a single night. Even
the opening and shutting of outside doors on cold winter
days may chill the mice considerably. The optimum condi-
tion is a room regulated between 70° and 80° F. both day
and night. Animals suffering slightly from exposure may
wheeze chronically, but appear in fair health and even breed.
This condition is known to the fanciers as "singing" or
"asthma."
Food. Food should be readily available to mice at all
times. A mouse that spends more than twenty-four hours
at one time without food is in grave danger of starving to
death. If only a meager amount of food is present, life may
be sustained, but the animals will not reproduce. A suitable
ration for mice measured by weight consists of:
240 parts rolled oats
30 parts powdered skim milk
8 parts cod-liver oil
1 part salt
A formula for rat feed, which is probably satisfactory also
for mice, has been recently prepared by Maynard (131)
consisting in parts by weight as follows.
56 LABORATORY MOUSE
Linseed-oil meal 15
Ground malted barley 10
Wheat red-dog flour 22
Dried skim milk 15
Oat flour 15
Yellow corn meal 20
Steam bone meal ' 1
Ground limestone 1
Salt 1
Total 100
As mice are so dependent for health upon the constant
availability of food, it is advisable to have present in their
cages at all times a balanced-ration dog biscuit upon which
they may gnaw if other food has been consumed between
feeding hours.
For mice to breed well, greens are desirable in the form
of lettuce or clover once or twice a week. Caution must be
observed in the feeding of lettuce that all tainted or rotten
spots be removed, for mice will eat these along with the
good portions and may be made sick by so doing. Hemp
seed is advised from time to time. According to fanciers,
animals suffering from lack of greens may become scurvied,
but this condition disappears when they are properly fed.
A Closed Feeding Can. Mice delight in digging in an open
dish full of food. They waste great quantities of food by
kicking it out of the dish, and contaminate with their feces
that remaining in the dish. In order to eliminate these two
undesirable features of the open feeding dish a closed feeding
can has been recently devised and is in use at the Bussey
Institution (see Fig. 11). This consists of a half-pound coffee
can approximately 4 inches high and Sh inches in diameter.
In the side of the can is cut a 1-inch square hole, the lower
edge of which is h inch from the bottom of the can. The top
and sides of the hole are faced with a strip of tin projecting
\ inch into the can, to prevent the fall of food near the
entrance. A wedge-shaped cage made of galvanized-wire
cloth of \ inch mesh is soldered in place with the large open
end of the wedge over the entrance and projecting about
THE BREEDING OF MICE IN LABORATORIES 57
2^ inches into the can. The edge of the wedge rests upon the
floor of the can and its sides extend outward on either side
of the opening from which they are about \ inch distant
laterally at the opening.
The cage is small enough so the hind quarters of the adult
mouse must remain outside the can while its hind feet rest on
the edge of the entrance. These features prevent both fecal
Fig. 11. Sectional view of feeding can.
contamination and the kicking of food out of the can. The
mesh of the screen-wire wedge is fine enough to prevent dry
ration containing rolled oats from sifting into the feeding
chamber. The mouse simply reaches through the mesh and
pulls down what food he desires, eats it in place, and backs
out of the feeder when satisfied. If it is desired to give the
Maynard ration in the closed feeder, it should be mixed in
equal parts with rolled oats, because the Maynard ration is
finely ground and sifts through the screen wire.
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BIBLIOGRAPHY
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^3T&
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