Genetics of the Norway Rat

810 Pages·1965·13.658 MB·English

by  Roy Robinson and G. A. Kerkut (Auth.)

GENETICS
OF THE
NORWAY RAT
BY
ROY ROBINSON
PERGAMON PRESS
OXFORD LONDON EDINBURGH · NEW YORK
PARIS · FRANKFURT
Pergamon Press Ltd., Headington Hill Hall, Oxford
4 & 5 Fitzroy Square, London W.l
Pergamon Press (Scotland) Ltd., 2 & 3 Teviot Place, Edinburgh 1
Pergamon Press Inc., 122 East 55th St., New York 22, N.Y.
Pergamon Press GmbH, Kaiserstrasse 75, Frankfurt-am-Main
Copyright © 1965
Pergamon Press Ltd.
First edition 1965
Library of Congress Catalog Card No. 64-19588
PRINTED IN POLAND
PREFACE
THE rat is one of the more extensively employed laboratory animals, yet—
somewhat surprisingly—hitherto there has not been available an account of
the genetics of the animal. It is true, of course, that the rat has often been
considered in a general fashion in volumes on animal genetics, and on occasion
the treatment has been fairly thorough. Unfortunately, more usually the
treatment has tended to be superficial, depending upon the competing interests
of the author or the scope of the volume. This state of affairs should not be
allowed to continue, and it is the intention of this book to review and to
provide a key to the considerable literature.
An attempt has been made to include all relevant material published prior
to 1962. In a number of fields it has been possible to include some important
work which has appeared at a later date. While every endeavour has been
made to achieve comprehensiveness only posterity can decide the success of
this aim. Each chapter is essentially monographic in tenor, with numerous
cross-references to pertinent aspects to be found in others. The research papers
cited should lead to a complete bibliography for the subject. While an effort
has been made to include the salient features of a piece of research work, it
should be recognized that the coverage may not be necessarily exhaustive.
Long discussion of techniques or extensive descriptions of non-genetical
matters have, perforce, been considered beyond the scope of this book. It is
irritating to find items of genetical interest, such as strain differences, in-
terspersed in a report, for example, devoted primarily to a pharmaceutical
analysis. Such items are extremely difficult to discover and bring to the notice
of the mammalian geneticist. The hint may be offered that a separate note
in a genetical journal, drawing attention to the strain difference, would not
come amiss.
It should not be thought that the subject matter of this book is only the
concern or the province of the mammalian geneticist—this is far from the true
situation. Any person who has to deal with living animals during any part of
his research is confronted with genetic variation of one form or another.
Hence, it is felt that the extent of the known genetics of the rat should be
within the cognizance of all biologists, especially those who employ the rat
at some stage of their work. If the reading of this book instils an added
awareness of a probable source of variation in experimental studies (as an
undesirable source of error or as a welcome extra dimension of analysis, as the
case may be!) one of its main purposes will be achieved. If this book encourages
an interest in the understanding of the nature of the variation, then this pur-
pose will be doubly achieved.
ROY ROBINSON
vii
ACKNOWLEDGMENTS
I SHOULD like to record cordial appreciation to the many people who have
assisted me in numerous ways during the writing of this book. I am indebted
to Drs. R. A. Beatty, W. E. Castle, T. C. Hsu, H. Kalter, D. Krech, S. Makino,
G. K. Manna, J. L. McGaugh, J. R. Nichols, R. D. Owen, E. Roberts, W. K.
Silvers, J. O. Sines, A. U. Smith, R. M. Stephan and J. Warkany for various
forms of assistance kindly accorded to me. I am particularly grateful to Dr.
P. L. Broadhurst for his help with many bibliographical matters. I am also
obliged to the many other investigators who generously sent me reprints of
their published research. I have to thank Mr. A. Coenders for the benefit of
his linguistic advice. Finally, my special thanks are due to Miss Hilda M. Perry
for her competent secretarial assistance.
INTRODUCTION
IN the eyes of the layman, the Norway rat is the laboratory animal par excel-
lence. In actuality, of course, the rat has to compete with other experimental
animals for its place in the laboratory. In this respect, however, the rat is fully
capable of holding its own: it adapts easily and quickly to congenial laboratory
routines, it is a convenient size for a vast range of experiments, it is docile and
completely tractable in experienced hands, it does not require large or expen-
sive cages and is renowned for reproductive proliferacy.
Along with other laboratory rodents at the turn of the century, the rat
was quickly taken up as a useful animal for establishing the general pattern ot
heredity. The early studies were largely directed towards the heredity of coat
colour but, as the genetic vista broadened, research with the animal began to
assume a wider variety. Some idea of the extent of this may be gleaned from
a perusal of the table of contents of this monograph. It is perhaps permis-
sible at this juncture to ponder upon the likely place of the rat in future
genetic research. The animal, of course, will continue to be useful for com-
parative rodent genetics. It will be especially valuable for meticulous study of
the aetiology of inherited malformations and diseases. The implications of
research of this nature for medical science is too obvious and important to be
overlooked or neglected. It is probable, too, that the rat will continue to
feature prominently in the field of psychogenetics. There are two reasons for
this belief: (1) the well-known regard for the rat as a psychological subject
and (2) the awareness of the need for information on the genetic aspects of
behaviour and intelligence. The genesis of animal behaviour could become as
important for psychology and psychiatry as the aetiology of malformations
in animals is for somatic medicine.
The extensive employment of the rat in many branches of science has
promoted the publication of numerous books on the animal. These books
have usually treated the animal in relation to one or a group of specific topics.
For example, for those seeking to establish a new rat colony, there is the
monographic account of Greenman and Durhing (1923) on the elementary
aspects of housing and feeding. In this connection, the first chapter of Farris
and Griffiths (1949) and the very informative books of Farris (1950) and
Worden and Lane-Petter (1957) should be consulted. The question of the
importance of a balanced diet for growth and reproduction of the rat has been
considered by Russell (1948). This tersely compiled bulletin is a mine of in-
formation on the dietary requirements of the species and reviews practically
all the work on the subject. There is also the interesting volume of Wiesner
and Sheard (1933) on the maternal behaviour. An important general source-
book is that of Farris and Griffith (1949), a well-known manual for informa-
1
2 GENETICS OF THE NORWAY RAT
tion on the rat and on the usefulness of the animal for research purposes.
A handy book of reference is that of Hagemann and Schmidt (1960), in which
considerable data has been brought together in the form of tables. Finally,
attention must be drawn to the classical work of Donaldson (1924) on the
biological form and function of the rat. The value of this early work of con-
sultation will probably never entirely cease so long as rats are bred.
The genetics of the rat have featured in a number of reviews from time
to time. The earliest of these were Lang (1914) and Wright (1917); to be
followed by Haldane (1927) and Castle (1947). In successive editions of his
book Genetics and Eugenics, which culminated in the fourth edition of 1930,
Castle has endeavoured to keep abreast of current research. A cursory
discussion of rat heredity may also be found in Castle's book on mammalian
genetics which appeared in 1940. Most of these reviews were largely concerned
with the inheritance of coat colour and texture. An exception was the
interesting but not wholly accurate epitome of Plate (1938); however, this
work did contain accounts of many genetic abnormalities. The most complete
discussion of the known hereditary malformations of the rat may be found
in the small but admirable volume of Grüneberg (1947a).
The rat appears to occupy a solid niche in the study of animal psychology.
A monumental amount of research is available on the animal and the total is
constantly being augmented. Many of the omnibus expository and review
volumes of experimental psychology have devoted one or more sections largely
to work accomplished with the rat. There are also the interesting accounts of
Lashley (1929) and Maier (1939); while special attention must be drawn to the
definitive surveys of Munn (1933, 1950). Although these two books have
different titles, they may be regarded as successive editions of the same work:
which thus provides a complete and succinct summary of published investiga-
tions on the rat. Hall (1951a) has commented that psychologists are gradually
coming to appreciate the importance of heredity in the interpretation of
their findings. The merging of the twin sciences of genetics and experimental
psychology may be seen in the coining of a new term to describe research
which uses the techniques of each: psychogenetics.
The importance of heredity in experimental biology may be put very
simply—so simply that its presentation could be overlooked as over-facile. The
phenotype of an organism is potentially determined by the genotype formed
at the moment of fertilization. Therefore, from one viewpoint, all traits are
determined completely by heredity. Alas, two subsequent processes stand
between this elementary viewpoint and the final outcome. Firstly, irregularities
in the ensuing development of the zygote which, perhaps, can be expressively
summed up as ontogenic error; and, secondly, the reaction of the geno-
type to the environment to which it is exposed. Both of these processes
are mutually interdependent and both are functions of the genotype. Thus,
a zygote becomes an individual which is unique since it is improbable that two
zygotes will have identical ontogenic errors or be exposed to exactly the same
environmental stimuli. Alas again, while these considerations may assist to
promote clear thinking they cannot decide the contributions of genotype,
INTRODUCTION 3
environment or ontogenic error in the expression of a given character. Only
careful experimentation can help in the clarification of this issue. The final
upshot is that however much it may be felt that a given character is de-
termined by exogenetic factors, the basic fact remains that the genetic com-
ponent of the variation may not be inappreciable. This fact is truly recognized
in many quarters, and many experiments are frankly organized either to
minimize the genetic differences or to exploit these very differences. In this
monograph, the evidence for genetic differences in response to various stimuli
will be singled out for emphasis. This procedure will be most apparent for
those reports which were not primarily concerned with the genetic implica-
tions of the results obtained.
Nomenclature of Rat Species
The zoological nomenclature of the rat remains essentially as set out by
H. H. Donaldson (1924). Generically, the designation Rattus has replaced the
obsolete terms Mus or Epimys, while at the species level, the name norvegicus
has priority over that of decumanus. The passage of time has given the designa-
tion of Rattus norvegicus to the Norway rat. The species may often be found in
the older literature, however, under one or more of the now obsolete
designations.
A cognate species to the Norway rat is the black rat. This particular rat
is of more than cognitive interest for three reasons. Firstly, because of the
close general resemblance between the two species, secondly, since the black
rat appears to have preceded the Norway rat in global migration and is in the
process of being displaced by the latter and, thirdly, because the black rat
displays a geographical variation of colour. The geographical variation of
colour has been regarded as sufficient justification for these to be ranked as
sub-species. Zoogeographically, this view may have some merit but, genetically,
the colour variation scarcely appears to warrant the status of sub-specification.
The black rat is also known as the house rat or roof rat, and all of the several
varieties are grouped into one species, Rattus rattus. Three primary categories
of sub-species are generally recognized. Rattus rattus rattus (black rat) with the
dorsum black and venter grey-black; associated with the cooler temperate
countries, especially those of Europe. Rattus rattus alexandrinus (Alexandrine
rat) with the dorsum brownish-black, venter grey, dorsal and ventral colours
merging gradually into each other; associated with Asia minor and North
Africa. Rattus rattus frugivorus (roof rat or tree rat) with the dorsum yellow
to reddish-brown, venter white or cream, dorsal and ventral colours sharply
demarcated along flanks; associated with the Mediterranean region and other
warm climates (Hinton, 1920).
Some doubt on the propriety of rigid adherence to the sub-speciation of
R. rattus has been mooted by Caslick (1956). This criticism is particularly
pertinent in those situations where two or more of the sub-species occur
together. Many localities in the North American continent appear to support
such co-existence. Caslick has given data which showed that rattus and
alexandrinus will interbreed and that the typical coloration of the two forms
4 GENETICS OF THE NORWAY RAT
was not lost as a result. The normal sub-species coloration was found to occur
in the same litter bred either from rattus X alexandrinus or from rattus X rattus.
Nicholson and Warner (1953) have shown that a similar inter-alternation
existed for alexandrinus and frugivorus on the Pacific island of New Caledonia.
Tokuda (1941) has concluded that the Japanese varieties of rattus, despite their
variation of coat colour, all belong to the same species. It appears reasonable
to propose that the black rat {rattus) differs from the Alexandrine rat
{alexandrinus) only in the possession of a dominant gene for extension of black
pigmentation. The evidence is conclusive in this respect and may be found in the
papers of Morgan (1909) and Feldman (1926). However, the difference between
these two species and some races of frugivorus is possibly a little more complex.
Yet, in those localities where a frugivorus type cohabits with rattus or
alexandrinus, the difference could arise essentially from a mutant allele of
agouti. Feldman found that two agouti alleles may exist, (i) agouti white belly
and (ii) agouti grey belly. These alleles could account for the difference in belly
colour between alexandrinus and frugivorus, while rattus could bear either
agouti allele. Symbolically, the genotypes of these varieties would be rattus
AWED or AED, alexandrinus AE and frugivorus AWE; where Aw represents the
white bellied agouti gene, A the grey bellied agouti, ED the dominant extension
of black and E the normal extension of black pigmentation.
Rattus norvegicus is less variable in coat colour than R. rattus. The colour
may be briefly described as greyish-brown on the dorsum and silvery-grey
on the venter, with possibly a tawny tint. Many wild populations are
dimorphic for a black variety which is probably homologous genetically with
the non-agouti mutant of the laboratory rat. It has been said that this black
variety may be confused with the black rat {R. rattus rattus). Hinton {loc. cit.)
has surmised that the melanic form of norvegicus may be on the increase and
affords a close parallelism with rattus, but there appears to be no direct evidence
for this surmisal. However, the observations of Watson (1944) on the incidence
of melanics in the dockland of London are of interest in this connexion. An
account of Watson's observations may be found in the succeeding chapter (see
Table 2).
It is advisable that the distinction between the norvegicus and rattus
species be based upon morphological characters and not upon coat colour. The
coat colour of the two rats is subject to variation, particularly for rattus as
described above, and the variation overlaps. The superficial differences between
the rats are useful for a rapid diagnosis and may be set out in opposition as
follows:
norvegicus rattus
Larger size, relatively stocky body. Smaller size, relatively slender body.
Muzzle blunt. Muzzle pointed.
Ear pinnae small, hairy, thick and opaque. Ear pinnae large, relatively hairless and trans-
lucent.
Tail stout, never as long as combined length Tail slender, often longer than the combined
of head and body. length of head and body.
Fur soft, with few harsh, bristly hairs. Fur soft, with many harsh, bristly hairs in
adults.
INTRODUCTION 5
Nipples: number varies from twelve to Nipples: number relatively constant around
fourteen. ten.
Pads on soles of the feet relatively small. Pads on soles of the feet relatively large.
Early History of the Rat
The early history of the two rat species has been outlined by Hinton (1919,
1920); and by Donaldson (1924) in some detail. There is no real evidence that
the Greeks or Romans were acquainted with the rat and it would seem
probable that the rapid multiplication of the animal to become an economic
pest is a phenomenon of modern civilization. The first rat to reach the
Western world was rattus. This species was thought to be indigenous to the
Indian peninsula and the spread westwards began as a consequence of the
opening up of trade routes with the East. It was not known to occur in
appreciable numbers in Western Europe before the twelfth century. The black
rat was carried to the Americas on the ships of the early explorers, probably
reaching both the North and South continents almost simultaneously, in the
sixteenth century. In North America, the more northerly regions appear to be
populated by rattus rattus, while in the warmer southern states, rattus alexandri-
nus has become the more common.
Rattus norvegicus apparently invaded Europe, again arriving from the East,
early in the eighteenth century. It was surmised by the early chroniclers that
it may have reached England somewhere between 1728 and 1730. The spread
of the Norway rat across Europe was probably very rapid, with reports of their
presence in the major capital cities following quickly in succession. Although
the invasion of the black rat preceded that of the Norway by several hundred
years, the latter soon almost completely displaced and exterminated the former.
This may be due to the fact that the Norway rat is the more powerful and
pugnacious of the two species; although the progressive disuse of wood in the
construction of buildings has been thought to be an important factor in
the deline of the black rat. The rattus species now survives only as small isolated
colonies in parts of Europe. The Norway rat apparently reached the North
American seaboard by about 1775, whence it soon began to supplant the black
rat and to take possession of all suitable habitats; mainly in the northern
latitudes. The natural home of norvegicus is said to be in the temperate regions
of Asia. To be more precise, the actual region may have been wild country
between the Caspian Sea and Tobolsk. It was possible that the animal extended
as far as Lake Baikal, where a sub-species (Rattus norvegicus primarius) has been
recognized. The Norway rat is very active and dominant in temperate
climates. In extremely cold areas, the rat can only exist in man-made shelters
and, in warm areas (for example, Asia), it is often unable to displace the rattus
species. The rattus animal, in general, is a more arboreal rat than norvegicus.
Hinton has remarked that at sea it is the principal ship rat as a consequence
of its superior climbing powers.
It appears almost certain that the Norway rat came into captivity as the
albino. Rat-baiting was a popular sport in England and France, as early as
1800, until it was prohibited some seventy years later. In this sport, between
6 GENETICS OF THE NORWAY RAT
100 to 200 recently trapped wild rats were placed into a pit and a trained
terrier was let loose among them. The spectators bet on the time required by
different terriers to kill the last rat. Large numbers of rats had to be caught
and held in readiness for these spectacles. Richter (1954) has written of the
existence of records which indicated that albinos were removed from such
collections of rats and retained for breeding and exhibition. From these prosaic
beginnings it was likely that individuals found their way into laboratories.
If the rats had been frequently handled from birth, they would likely be
semi-tame and relatively tractable for experimental purposes.
According to Richter (1950, 1954) the first paper on the employment of
rats in the laboratory was that of Philipeaux (1856) on the effects of adre-
nalectomy. Unfortunately, it is not known if these rats came from an
established colony. The animals were referred to as albino R. rattus in the
original paper but this was probably an error. From this time onwards there
were sporadic accounts of rats being used for various experimental work.
However, there appeared to be no systematic attempt to found colonies or to
arrange for a supply of breeding animals. The first breeding experiments on the
rat were those of Crampe (1877-85) with albino and wild rats. Dr. H. H. Don-
aldson, who has devoted his whole life to a study of the animal, was first
introduced to the rat in 1893 (Conklin 1939). The rat was apparently first
employed in psychological research by Steward (1898), Kline (1899) and Small
(1900); see Miles (1930) and Warden (1930). Since that time the rat has been
utilized for psychological research on an ever expanding scale. An idea of the
impressive amount of work on the rat may be found in the two books by Munn
(1933, 1950). In the last few decades an increasing amount of attention has
been given to the nature of the genetic basic of the complex behaviour of the
rat. The initial impetus for this work was an attempt to gain some insight into
the temperament of the rat. This field has proved to be involved to the extreme
and has demanded a much closer coming together of genetic and psychological
techniques.
Interspecies Hybridization
The various rats discussed in the preceding section are so similar in outward
appearance that it has long been thought that the two species should be capable
of hybridization. Even if the hybridization did not occur in nature, it may be
possible for the hybrid to be secured under artificial conditions. However, these
expectations have not been substantiated in practice. Fortunately, reports of
alleged hybrids between species of rats do not appear to have reached the
proportions of those for the notorious Leporide, the mythological hybrid
between the rabbit (Oryctolagus cuniculus) and the hare (Lepus europaeus);
see Robinson (1958). Adams (1957) has since shown that rabbit ova
fertilized by hare spermatozoa perish at the late morula or early blastocyst
stage of development. There was even some doubt whether the hare spermatozoa
actually contributed any hereditary material to the rabbit ova or if the ova was
merely stimulated into development by the entry of the spermatozoa.
The claim has been made by Van Kempen (1899; see Craft 1938) to have