Genetica (1972) 43:239-243

GENETIC STUDIES OF THE SYRIAN HAMSTER.

VIII . THE SEX-LINKED GENE TORTOISESHELL

RoY ROBINSON

St. Stephens" Road Nursery, Ealing, London, W. 13

(Received November 2, 1971 ] Accepted November 5, z97z)

The occurrence of sex-linked yellow is described and designated as tor- toiseshell (symbol To). The phenotype produced by the heterozygous female (To+) is a mosaic of that of ToTo and + +. Genetic inactivation of one X chromosome per cell is thus indicated. The To gene interacts phenotypically with genes Ba, Ds and Wh.

Introduction

With the possible exception of the house mouse, sex-linked genes

in mammalian species are still sufficiently uncommon to excite

interest. About sixteen mutant loci have been reported for the mouse

(ROBINSON, 1972). The Syrian hamster is known to have three sex-

linked genes to date: mottled (Mo; MAGALHAES, 1954), tortoiseshell

(To; ROBINSON, 1966) and hind-leg paralysis (pa; NlXON & CON-

NELLY, 1968). The present report describes the more interesting

aspects of the phenotypic variation displayed by the tortoiseshell

gene. Full details of the various mutants cited may be found in

ROBINSON (1968) and NIXON et al. (1970).

Origin and description

The first mutant animal to be observed (circa 1964) was an agouti

with a patch of yellow fur bred from normal parents. She was mated to

a normal male and produced three normals, one female with a yellow

patch and a yellow male. The latter was immediately recognized to

be a phenotype new to the hamster.

The hemizygous male (To) and homozygous female (ToTo) have the same phenotype. Both are orange-yellow in colour, noti- ceably darker on the dorsum than on the venter, with a fine sprinkling

2 4 0 R O Y R O B I N S O N

of dark guard hairs. No animal has yet been seen without these guard hairs although the quantity is variable. The guard hairs give the young yellow nestling a characteristic dusky appearance. In the young hamster, the undercolour of the coat is pale cream but this darkens to bluish with age, the darkening keeping pace with the deepening of the yellow coloration of the juvenile to the yellow- orange of the adult individual. The elimination of eumelanism applies only to the hair, for dark pigment develops in the skin in amounts comparable to that found in the normal agouti (ear pinnae, palpebrae and hip glands of both sexes; prepuce and scrotum of males; perineal of females). The heterozygous female (tortoiseshell; To+) is a parti-coloured mosaic of yellow and agouti, the yellow areas corresponding in phenotype to the homozygous genotype.

Genetics

The inheritance of To is shown by Table I. The transmission is that of a typical X chromosome borne gene, as shown by the Z 2 values in the last column (none of which are significant). In calcu- lating the X2s, the occurrence of the unexpected type ( + + ) females has been ignored. It is clear that the incidence of these exceptional animals is too low to seriously distort the expected ratios of the various phenotypes. These females could arise from two causes; either by misclassification ot sex or by the To+ phenotype over- lapping that of type. The latter possibility is judged to be the most likely explanation. Indeed, misclassification of sex is ruled out for the last cross of the table, yet five type females were observed.

T A B L E 1

P R O G E N Y F R O M C R O S S E S W I T H T H E To G E N E

C r o s s lV[ales F e m a l e s

f~ To + ToTo To + + + X 2

+ ToTo 7 5 - - - - 6 l 7 2.2

+ To+ 4 9 6 5 - - 4 9 6 9 5 . 8

To ToTo 4 7 - - 3 9 - - - -

To T o + 1 9 4 166 173 183 3 4 2 . 5

To + + 4 8 - - 3 2 5 3 . 2

T O R T O I S E S H E L L IN S Y R I A N H A M S T E R 241

Discussion

The To gene possesses a number of interesting features, particularly for the tortoiseshell form To+ and for phenotypic interactions with other mutants. The tortoiseshell is a mosaic of yellow and agouti but seemingly predominantly agouti. So far, attempts to increase the

amount of yellow have been unsuccessful. The yellow areas occur in the main as small patches and streaks on any part of the head or

body. Usually, several patches occur on the same individual but the

variation is such that the patches may be single and be so small to almost escape detection. The occurrence of exceptional normal

agouti females indicate that some To+ animals may have the yellow areas so intermingled with the agouti to be undetectable or be devoid

of patches. The tortoiseshell pattern has been cited as an example of X chro-

mosome inactivation (LYON, 1962; ROBINSON, 1968). However, the

preponderance of the agouti areas in the pattern requires an expla- nation. If X chromosome inactivation in the primordial melanoblasts

is strictly at random, the occurrence of almost all-agouti animals

should be matched by the occurrence of almost all-yellow. These latter have not been positively identified. Tortoiseshells have been bred however, which were so yellow to appear as sandy-agoutis, but tend to be infrequent. Despite the above remarks, there is at present no compelling reason to think that the inactivation is not at random (LYON, 1966, 1968). Granted this initial premise, the implication is either that the yellow cell lineage is incapable of as rapid proliferation

as the agouti or that the contiguous agouti cells are able to influence the yellow. There is a third explanation for the present situation.

The dark coloured agouti hairs may be able to obscure the yellow so that a 50:50 per cent mixture is agouti and the percentage of yellow hairs may have to be very high before the area ceases to be sandy-

agouti and is clearly yellow. Such animals will be detected as tor- toiseshell and the effect will be to shift the spectrum of variation towards the agouti end of the scale.

The tortoiseshell pattern displays no interaction with piebald (s)

except, on an abservational level, to make the tortoiseshell phenotype less easy to identify. On the other hand, there is noticeable interaction of the pattern with white band (Ba). The number and particularly the

242 ROY ROBINSON

size of yellow areas is increased in Ba+ To + females. This difference of interaction of To+ for the two white spotting genes may be related to the nature of the spotting. In ss individuals, the spotting is irregular, much broken up and occurs over most of the body, whereas, in Ba individuals, the spotting is usually not broken up and restricted to the mid-region of the body. That is, the spread of Ba spotting is more regulated during embryonic development. It may be that the regu- lation facilitates the separation of + and To cells and a likely mecha- nism by which this could be achieved is by limiting the number of sites giving rise to primordial melanoblasts. Even if the To cells do proliferate less rapidly than + , the lack of competition would produce larger yellow areas. An interaction of tortoiseshell with dominant spot (Ds) has been noted by NlXON et al. (1970). There is distinct separation of the yellow and agouti areas. It is of interest that the white spotting produced by Ds tends to be localized (head, chest, venter) but not so obviously as in the case of Ba.

An autosomal cream or non-extension of eumelanism (e) has been known in the hamster for about two decades. This form differs from ToTo by being lighter in colour and lacking the blue undercolour and dark guard hairs. The e gene is epistatic to To, so that eeTo, eeTo+ and eeToTo are all phenotypieally ee. Genes e and Wh (anoph- thalmic white) interact to produce an extreme pale creamy white animal for the genotype eeWh+, in contrast to cream (ee) and white bellied agouti (Wh+). A similar interaction occurs between To and Wh. The genotype ToToWh+ is off-white to pale straw-yellow in colour, with a fine sprinkling of dark guard hairs.

There is no known homologue among mutants of rodent species for tortoiseshell. However, the apparent homology between tortoiseshell and sex-linked orange (0) of the domestic cat is striking (ROBINSON, 1968). It is of interest that 0 interacts with S (dominant piebald spotting) to transform a brindled tortoiseshell cat, where the yellow and agouti areas are intermingled, into one where the yellow and agouti areas are larger and occur as a distinct patchwork (NORBY & THULINE 1965). This behaviour parallels the observations for the tortoiseshell hamster. I t may be noted that piebald spotting of the cat tends to be continuous (not broken up) and thus resembles Ba rather than s in this respect. The mechanism of separation of the yellow and agouti cell lineages may be identical in the two species.

TORTOISESHELL IN SYRIAN HAMSTER 243

T h e a b o v e o b s e r v a t i o n s were m a d e i n d e p e n d e n t l y of t h o s e of

NIxON e t al. (1970) a n d con f i rm t h e i n t e r a c t i o n s for T o w i t h o t h e r

m u t a n t s d e s c r i b e d b y t h e s e au tho r s .

Thanks are due to Mr. PERCY XV. PARSLOW for part of the early data.

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LYon, M. F. (1966). X chromosome inactivation in mammals. Adv. Teratol. 1 :

25-34. LYon, M. F. (1968). Chromosomal and subchromosomal inactivation. Ann. Rev.

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MAI-IALHAES, H. (1954). Mottled white, a sex-linked mutation in the golden hamster, Mesocricetus auratus. Anat. Rec. 120: 752.

NIXON, C. W., J. 14. BEAUMONT • M. E. CONNELLY (1970). Gene interaction of coat pat terns and colors in the Syrian hamster. J. Hered. 61 : 221-228.

NIxoN, C. W. & M. E. CONNELLY (1968). Hind-leg paralysis: a new sex-linked mutation in the Syrian hamster. J. Hered. 59: 276-278.

NORBY, D. E. & H. C. THULINE (1965). Gene action in the X chromosome of the cat. Cytogenetics 4: 240-244.

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