Mutations in Gerbil Coat Colour~Part 1
Today's Mongolian gerbil that we keep as a pet, descended from 20 pairs that were caught in 1935 by Dr. C. Kasuga, in the Amur River basin, Eastern Mongolia. The foundation pairs were then bred in Japan to increase their stock for use in laboratories. In 1954, five males and four females were sent to Tumblebrook farm, Inc., Brant Lake, N.Y. and bred for uniformity. It is these 9 gerbils that formed the nucleus of the breeding stock for the USA and Europe. (Schwentker, 1963, 1968; Marston 1972)
The original captive gerbil population all possessed 'agouti' or wild coloured coats. The foundation stocks, and their wild counterparts, would have also been carrying the normal amount of dominant coat colour genes at all the relevant coat colour loci, and are described as 'AACCDDEEPPUwUw'. Geneticists often simply use '++' to denote the normal wild colour agouti. Our domestic 'Golden' agouti gerbils today are commonly referred to as 'AA' when homozygous, but most Agoutis we come across will most likely carry recessive colour genes because since their introduction as a pet, several mutations have occurred.
Because of a recessive mutation at the Agouti locus, not only can they be 'AA', but they can also just as easily be 'Aa', or in the case of the black gerbil (non-agouti) mutation, 'aa'. When we are uncertain of the ancestry of our domestic golden agouti gerbils we tend to use the notation 'A-C-D-E-P-Uw-' because until we test breed the gerbil we are unsure of which recessive coat colour genes it carries, so will use a dash, dot or an asterisk as a form of shorthand notation when we are unsure of the gene at each particular locus.
It wasn't until 1971, nearly 30 years later after its introduction into captivity, that the non-agouti mutation appeared in the gerbil. At this time only a few mutations were known; these were the Dominant spotting mutation and the Himalayan mutation.
References
Schwenker, V. 1963. The gerbil. Ill. Vet., 6:5-9.
Schwentker, V. 1968. The care and maintenance of the Mongolian Gerbil. Tumble-brook Farms, Inc., Brant Lake, New York. 27 p.
Marston, J.H. The Mongolian gerbil. In: The UFAW on the care & management of laboratory animals. Essex: Longman; 257-268
The Chinchilla or the Albino locus is responsible for the overall level of colour produced in the gerbil's coat. It effectively controls a crucial piece of the pigment pathway responsible for forming the pigments within cells. Mutations occurring on this locus which are responsible for two commonly occurring coat colours in domestic animals, the first being the albino; a white furred animal with pink eyes; the other coat colour being the chinchilla; a grey furred animal. This mutation allows black pigment to be produced in the coat, but the yellow pigment is severely reduced. The chinchilla mutation is very variable amongst domestic species, both in the intensity of the black pigment, and also the amount of yellow left in the coat. Both the albino and chinchilla are recessive mutations occurring at the C locus. However neither of them has appeared in the Mongolian gerbil. White gerbils with pink eyes do exist but are the result of a combination of diluting genes and are known as "pseudo albinos". However, it is still genes at the C locus that are key factors in producing these combinations.
A true albino would be 'cc', but as of yet none have appeared in the Mongolian gerbil. Only two intermediate alleles have occurred on this locus, these being Himalayan ( c(h) ) and Chinchilla medium ( c(chm) ), which we will discuss further below.
It is worth noting that there was a report of albino gerbils in the scientific literature, (Matsuzaki, et al., 1989). The paper is quite controversial and presents three loci in gerbils for discussion, these being the A-locus, B-locus and C-locus. The gerbil colony under investigation was well established and a total of 1855 gerbils were bred over a 39 year period, from 1949-1988. During this period they introduced four white coated gerbils that were discovered in a pet shop in Yokohama. These white gerbils were proven to be carrying the black mutation. Further breeding showed that both white and black were recessive traits in the gerbils. The authors of the paper then went on to say that this was the first report of a black coat colour mutation which was incorrect because black gerbils had previously been described in the scientific literature (Cramlet et al. 1974; Waring, et al., 1980; Henley & Robinson, 1981; Allan & Robinson, 1988 ). The authors of the paper then also claimed that the white gerbils under investigation were 'cc' or albino and not the DTW acromelanistic gerbils as previously described (Robinson,1973), nor was pink-eyed dilution or other modifying factors taken into account. Of course, it cannot be discounted that this 'cc' mutation has been lost, however it is an unlikely assumption. The authors of the paper, as well as reporting the white gerbils as albinos, also hypothesised on a brown locus that controlled the amount of melanin in the black gerbils they studied, but to this day, no brown locus has ever appeared in the gerbils to confirm this hypothesis.
Two mutations do occur on the C locus in the Mongolian gerbil, these being Himalayan c(h) and Chinchilla Medium c(chm). Himalayan is the earliest of the known colour mutations in the gerbil, and first appeared in the late 1960's; Chinchilla Medium appeared much later in 1994. It was designated the name Chinchilla Medium because of its close similarity with the sable coat colour in the rabbit. ( Petrij et al, 2001) It should be noted though, that its old name was originally "Burmese" because it was instrumental in producing the Burmese coat colour variety in the Mongolian gerbil, however, the effect of the gene in the gerbil is reasonably dissimilar from the Burmese allele c(b) in the cat, even though both genes are mutations on the C locus. Both mutations in the gerbil are inherited recessively, and both are acromelanic (acromelanism literally means "coloured ends") and as such they are both temperature sensitive genes.
In true albino animals the pigment pathway is totally broken, and this leads to the animal being unable to produce pigment anywhere in the body. This in turn leads to white fur, pink eyes and translucent nails. In this case, a mutation in the enzyme tyrosinase is rendered completely non-functional, and as such, no pigments are produced. In gerbils however, the mechanism which produces the pigments in c(h) and c(chm) type gerbils is semi-functional, and as such is very fragile and temperature sensitive, so wherever the temperature is too high, little or no pigments are produced. This is the reason why the colourpoint gerbils have full colour in the cooler regions of the body, such as the ears, nose, feet and tails, when compared to the lighter colouring in the warmer regions of the body. The Himalayan mutation is a pronounced version of this gene, being severe in reducing the coat pigments when compared to Chinchilla Medium , and it is only the tail and very rarely the ears that show any pigmentation. So, any mutation in the enzyme tyrosinase (the C locus) can be very wide ranging, from completely non-functional, in which case we get an albino animal which has no pigment whatsoever, to minor reductions in pigment when the gene is semi-functional, and this semi-functionality can also have a very wide spectrum too, all of which can then give rise to phenotypes such as the Siamese, Burmese and Himalayan coat colour varieties. (Kwon et al. 1989.)
There is also another factor that can further modify a gerbils coat colour at the C locus, and this is known as Dominance modification. This effect occurs with the recessive genes at the C and P locus. The normal dominance hierarchy of alleles at the C locus are modified when there are two recessive alleles at the P locus ('pp'), i.e., if the gerbil is red-eyed. Rather than the full colour expression, with C being completely dominant over the lesser alleles, it becomes incompletely dominant, allowing the c(h) and c(chm) alleles to be expressed. This creates paler forms of the 'A- CCpp' (Argente Golden). These being 'A-Cc(h)pp' (Argente Cream) and 'A-Cc(chm)pp' (Argente fawn or Topaz). The same coat colour effect occurs on a non-agouti (Black) background as well, where Lilac ('aaCCpp') becomes Dove ('aaCc(h)pp') or Sapphire ('aaCc(chm)pp'). The Sapphire shade is in-between Lilac and Dove in colour.(Leiper, B.D. & Robinson, R. 1984)
A similar effect to this also occurs with the C alleles when combined with 'ee', where c(h) and c(chm) effectively lighten the coat producing lighter versions of DEH's and Nutmegs.
In the Mongolian gerbil, pink-eyed dilution and Chinchilla, are known to share genetic linkage, meaning that both genes are located on the same chromosome. (Leiper & Robinson, 1986) So, just like the mouse, where the original P mutation and a mutation of the tyrosinase gene (C locus) were used to define the first genetic linkage groups ( Haldane et al. 1915), again holds true for the Mongolian gerbil, and helps play an important role in the understanding of the basic aspects of mammalian genetics.
Also as a quick aside, A gerbil that carries two copies of either c(h) or c(chm) along with pp, will always be white all over with pink eyes, regardless of the other colour genes carried (pseudo albino). However if a gerbil is c(h)c(h)PP or c(h)c(h)Pp (We know the presence of at least one P gene stops one c(h) gene having any effect) a pair of c(h)c(h) genes, or when the recessive mutation is in a homozygous state, will create the Dark tailed white, or Himalayan gerbil. The presence of the dominant dark eyed genes doesn't produce a dark eyed gerbil as we might expect, as the Himalayan gene in its homozyous state will almost completely mask the effect of all the other known colour genes...but not quite, as it leaves the animal with some pigment in the form of a dark tail.
References
Matsuzaki, T., Yasuda, Y. & Nonaka, S. 1989. The genetics of coat colors in the Mongolian gerbil (Meriones unguiculatus). Experimental Animals, 38, 337-341.
A second Acromelanistic Allelomorph at the Albino Locus of the Mongolian gerbil (Meriones unguiculatus) F.Petrij, K,Van Veen, M.Mettler, V.bruckman.- The Journal if Heredity- 2001:92(1)
Haldane. J.B.S., A.D. Sprunt, & N.M. Haldane, 1915 Reduplication in mice. J. Genet. 5: 133-135.
Leiper, B.D. & Robinson, R. 1984. A case of dominance modification in the Mongolian gerbil. The Journal of Heredity, 75, 323
Cramlet, S.H., Toft II, J.D. & Olsen, N.W. 1974. Malignant melanoma in a black gerbil (Meriones unguiculatus). Laboratory Animal Science, 24, 545-547.
Waring, A.D. & Poole, T.W. 1980. Genetic analysis of the black pigment mutation in the Mongolian gerbil. The Journal of Heredity, 71, 428-429.
Henley, M. & Robinson, R. 1981. Non-agouti and pink-eyed dilution in the Mongolian gerbil. The Journal of Heredity, 72, 60-61.
Allan, D. and Robinson, R., 1988. Assortment of coat color genes in the Mongolian gerbil. Journal of Heredity, 79(5), 386-7.
Robinson, R. (1973). Acromelanic albinism in mammals. Genetica 44, 454-458.
1986. Linkage of albino and pink-eyed dilution genes in the Mongolian gerbil and other rodents.- Leiper, B.D. & Robinson, R. 1986. - The Journal of Heredity, 77, 207.
Kwon BS, Halaban R, Chintamaneni C. 1989. Molecular basis of mouse Himalayan mutation. Biochem Biophys Res Commun. 161(1):252-260
The mutation on this locus occurred in 1997, and was tentatively assigned the symbol "d" by geneticists. However, although no scientific literature has been published on this gene, there is a brief mention of an unpublished report on the new diluting gene by Pund & Petrij in the published report on recessive and fading yellow in the Mongolian gerbil (Petrij et al.,2007)
In the Mongolian gerbil, the dilute gene is inherited recessively, and gerbils that are homozygous for this gene have less intense or diluted fur. the 'dilution' effect is not due to a reduction in the amount of pigment in the hair. In fact, D locus mutations produce fur which have on average more hair pigment than non-dilute animals. This is the case for true d/d animals (Maltese dilution) irrespective of whether the mutation is on a yellow or a black background ( Brauch and W. Russell, 1946; E. Russell, 1948). The diluted phenotype is brought about because around one-third and two-thirds of the pigment is deposited into a few very large, conspicuous clumps with clear-cut edges, and these large clumps of pigment have little effect on light absorption ( E. Russell, 1948; Grüneberg, 1952).Therefore the light is reflected in a different way off the hair. This effect is noticeable, and creates a 'washed out' appearance to the fur. (Searle, 1968)
In the Mongolian gerbil this diluting gene is distinct, and dissimilar in several ways from the dilute gene in the mouse (Maltese dilution) where it dilutes all pigments equally, in the Mongolian gerbil it is much more effective at diluting black pigments and ineffective at diluting yellow pigment. The effect of the gene on a yellow background is minimal, and any pigment lost, subsequently returns in older gerbils.
However, similar to the D locus mutations in most domestic species, the gene does produce the well known coat colour variety of 'Blue' ('aadd') which is in essence a modified black coat colour variety. After saying this, it is also worth noting there exists several known genes that are blue fur mimics on a non-agouti background, and not all animals that display blue fur are necessarily showing a mutation at the D locus.
References
Petrij F, M. Mettler M, V. Brückman V, van Veen K, Recessive yellow in the Mongolian gerbil (Meriones unguiculatus). Journal of Experimental Animal Science 43 (2007) 319–327.
Brauch, L.R., and Russell, W.L.: Colorimetric measurement of the effects of the major coat color genes in the mouse on the quantity of yellow pigment in extracts. Genetics 31: 212, 1946
Russell, E.S.: A quantitative histological study of the pigment found in the coat-color mutants of the house mouse. II. Estimates of the total volume of pigment. Genetics 33: 228-236, 1948.
Grüneberg, H.: The Genetics of the Mouse, 2nd ed., Nijhoff, The Hague, 1952.
Searle, A.G.: Comparative Genetics of Coat Colour in Mammals, Logos Press, London, 1968.
The E locus is named the Extension locus, because mutations that occur here cause the extension of the yellow pigments or conversely the black pigments in the fur. There are a range of mutations at the E locus in other domestic species, and the mutations normally work alongside the agouti locus to dramatically increase the length of the yellow banding in the hair shaft. Mutations on the E locus that are dominant to the wild type (Agouti), will make the animal completely black, where as recessive mutations extend the yellow pigment in the hair shaft, sometimes covering all, or almost all of the hair. There also exists another mutation at the E locus that is recessive in nature, and is very unusual in its actions. This gene is responsible for the bi-coloured 'harlequin' or 'Japanese brindling' coat colours in the rabbit, and 'tortoiseshell' or 'brindle' coat colours in the cavy. This gene, (e(j)) the 'j' being short for Japanese, has yet to appear in the gerbil.
The extension gene encodes a melanocortin receptor (MC1R) which is a melanin stimulating hormone receptor (Robbins et al., 1993). In loss of function mutations of this gene, it causes a continuous production of the red/yellow pigments (phaeomelanin). Other mutations that cause the gene to be hyperactive bring about an exclusive production or brown/black pigments (eumelanin). (Jackson, 1993; Barsh 1996)
In the Mongolian gerbil, two mutations have occurred at the E locus, both being recessive in nature. The first mutation, extension of yellow (e), appeared first in the U.S.A in the mid 1980's, but its appearance was very poorly documented. Surprisingly, a little later, an identical mutation occurred again in Poland. In March, 1993, Dr Fred Petrij, a member of the Gerbil Genetics Group received several gerbils carrying this mutation. Initially they were being kept at Poznan zoo as an unknown gerbil species, but he could find no further information regarding their origin. Karyotyping at the University of Lübeck in Germany was undertaken, as were taxonomic investigations at the Museum Alexander Koenig, Bonn, Germany, where type specimens of the Mongolian gerbil are kept. The conclusions of these studies, plus further breeding studies, showed the gerbils to be conspecific with Meriones unguiculatus, and they represented a new mutation of the Mongolian gerbil (Petrij et al., 2007)
The effect on the Golden Agouti coat brings about a yellow furred gerbil with a dusting of fine black ticking. However, because the mutation only changes the way that pigment is produced in the hair shaft, and not elsewhere, both the skin and the eyes retain their dark pigments.
Extension of Yellow on an Agouti background (A-ee) produces our Dark-Eyed Honey coat colour, but the effect of the gene is unusual when displayed on a non-agouti (black) background (aaee). In many other domestic species, 'aaee' produces a yellow coat, the 'ee' effectively masks 'A' and also 'a'. So, 'A-ee' and 'aaee' will be almost the same colour. The effect can be shown in animals such as mice, cavies, Syrian hamsters and even horses. In other species, such as the rabbit, and similarly the gerbil, the 'e' gene is incapable of removing all of the black pigment produced by non-agouti. In the rabbit it produces a 'sooty yellow' coat colour ('aaee'), which leaves black pigment around the muzzle, eyes, ears and stomach.( Robinson, 1978) In the gerbil, Extension of Yellow effectively masks black pigments when they are juvenile, and the pups are a deep orange/yellow colour, but as the gerbil moults and becomes an adult, this masking no longer takes place, and some black pigment returns to the hair shaft, producing the Nutmeg coat colour.
Another unusual effect with Extension of Yellow occurs with ageing. With Dark-Eyed Honeys (A-ee), there are more subtle coat changes occurring each time the gerbil moults, and as the animal ages, the point at which the white bellow shades into the yellow top coat colour recedes upwards along the flanks of the gerbil. Older gerbils can sometimes appear to have a stripe of the original colour, with a lighter colour shade down their flanks.
The second mutation at the E locus in the gerbil is Fading Yellow (ef). The 'f' being short for fading. This mutation first occured in the U.S.A around 1980 but its origins were obscure. This mutation also appeared again at a later date and was discovered in an Austrian pet shop by V. Brückmann, a Gerbil Genetic Group member. (Petrij et al., 2007) The common name for the coat colour is Schimmel, a German word meaning "to moult" or "to mould". Both 'AAe(f)e(f)' and 'aae(f)e(f)' gerbils are yellow, but with each successive moult, the coat colour fades to an off-white colour. Yellow Pigment is retained only on the tail and nose region. The mutation is recessive to Extension of Yellow (e), but the Extension of Yellow mutation isn't completely dominant over Fading Yellow ( e(f) ). This means that a gerbil that is 'ee(f)' will tend to be a slightly lighter shade than one that is 'ee'. One other effect of this is that the 'ee(f)' gerbil will get lighter coloured or off-white, irregular patching on its fur as it ages.
References
F. Petrij et al., Recessive Yellow in the Mongolian Gerbil (Meriones unguiculatus) Journal of Experimental Animal Science 43 (2007) 319–327
Robinson, R., 1978. Colour Inheritance in Small Livestock. Fur and Feather, Bradford.
Barsh, G.S., 1996. The genetics of pigmentation: from fancy genes to complex traits. Trends Genet. 12,
299–305.
Jackson, I.J., 1993. Colour-coded switches. Nature 362, 587–588.
Robbins, L.S., Nadeau, J.H., Johnson, K.R., Kelly, M.A., Roselli-Rehfuss, L., Baack, E., Mountjoy,
K.G., Cone, R.D., 1993. Pigmentation phenotypes of variant extension locus alleles result from point
mutations that alter MSH receptor function. Cell 72, 827–834.