White Markings

I chose to work with marked animals because they are beautiful animals, but also because there is a need for improvement and development of marked lines, and it is a challenge that requires knowledge of genetics and good record-keeping.

Any breeding program requires a bit of knowledge, monitoring the health of lines, perfecting tints of color, getting attractive "typey" animals, etc. White markings, however, provide additional challenges.

One "problem" is that marking genes can cause different effects with minor modifies, and one genotype can look almost identical to another. There are different loci of genes that interact in different ways. When you cross rats from different lines, there is virtually no way to predict the markings they will produce.

Another problem is the nomenclature of markings. We have one word for "Berkshire" even though they might have considerable differences in the amount and placement of white and are often caused by different genes. We also call any number of markings "mismarked capped" or "mismarked hooded" even though different genes might be involved, and it might be entirely predictable if such differences were well-described. And what you call "self" even if it looks "self" may genetically be an Irish or Berkshire.

Also most markings are not simple recessive and dominant. They interact to produce different effects. And some of these genes are even lethal when homozygous.

One of the most crucial considerations is the close relation of the pigment genes (particularly those that cause white markings) to the genes that control the central nervous system. During embryonic development the cells that produce skin pigment are in close proximity to the ones that will form the central nervous system. A mutation that prevents pigment attachment (which is how white markings are formed) sometimes also causes changes in the nervous system. This is what caused megacolon and megacecum in rats (also deafness in white cats and dogs). Such mutations are usually related to face markings. But problems in the nervous system don't always affect the pigment, and white face markings aren't always linked to megacolon.

The H-locus

The original pet/fancy rat lines' markings are caused by mutations on what we call the "hooded" locus. The best known of all these mutations is "hooded" and it was the first mutant allele known. Hoodeds are considered the "safest" of all markings, as the mutation is not associated with any health problems, and the hooded phenotype is easy to distinguish from other markings (including similar ones like banded). These gene definitions come from a few resources including the now non-existant Rodentfancy.com (I am not listing any genotypes here because none of the references I found echoed what I've seen in breeding.)

H: Self gene; Involved in self, Berkshires, Irish, and possibly variegated
h: Hooded gene; Homozygous is hooded, also in Berkshires, Irish, and possibly in barebacks and capped
He: Extreme hood gene; In Berkshires, also capped, patched, BEW, and capped
Hre: Restricted hood gene; Homozygous lethal, fades colors and causes odd-eyes, sometimes sterility in males
Hro: Roberts gene; Homozygous lethal, fades colors and causes odd-eyes
hn: Notched gene; Similar to He but always a notch at the back of a capped marking
hi: Irish gene; Mock selfs, Irish, and "Berkshire," also in variegated, and sometimes hooded
hdu: Downunder gene; Homozygous lethal, causes colored parts to be on the underside (sometimes called "double hooded")

Megacolon-linked Genes, etc.

Most other marking genes in the United States are linked to mecacolon/megacecum. The UK has a few marking genes similar to US in looks but not associated with this disease. I won't list those here, because I am not familiar with UK lines or why those types of markings don't have megacolon links.

It is important to note that megacolon is a very complicated disease. It is not a simple genotype = phenotype issue. Megacolon varies in penetrance (penetrace = whether the individual has the phenotype and the extent of the phenotype). These genes might only result in megacolon 10% of the time or even less. (Some breeders find this acceptable. I do not. Propogating megacolon genotypes should not be done at all, in my opinion.) Animals with a mild form of megacolon (only a small portion of gut affected) might not show symptoms until later in life (severe cases kill pups just after weaning). Some fairly recent studies found that double mutants and even carried genes in combination can cause an increase in both the occurence and severity of this condition (Cantrell et al. 2004, McCallion et al. 2003). This explains how two lines that appear healthy, when crossed, produce pups with megacolon. Megacolon also shows a sex bias and other trends that show it is related to many factors in development. In human beings the disease is not always genetic or hereditary, but in rats, it is, which means rat breeders can breed lines completely free from megacolon -- as long as they practice selectivity and never breed animals known to produce MC or from litters that contained it.

Here are some of the genes and their mutations:

Sox10: has a dominant mutation "Dom" that is not known for extensive spotting. Megacolon occurence varies in penetrance.
EdnrB: two recessive mutations are known at this locus, "s" (spotting) and "sl" (spotting lethal). "sl/sl" show a high degree of spotting, similar to patched, dalmatian, or BEW markings. "s/s" show less spotting. "sl/sl" has high penetrance with most (though not all) pups with the genotype having the condition.
Ret: the recessive mutation "-" shows very high penetrace in both occurence and severity and affects nearly all individuals with the genotype. It was also shown to have a dosage effect (causing MC when carried) in combination with other genes (Cantrell et al. 2004).
Other Genes: I have not read papers on these yet, so am not sure of these effects, but mutations on 5 other genes were identified in Hirschsprung patients (Hirschsprung's disease is human megacolon): GDNF, NRTN, EDN3, ECE1, and SMADIP1.

Most rat breeders are not aware of the nature of this disease, and it is not certain which mutations are present in pet/fancy lines. So heated debates do persist among breeders due to incomplete penetrance and multiple genes. Some say since it is "dominant" (possibly refering to the "Dom" mutation?) it will die out naturally. This is not true. Incomplete penetrance means rats with the genotype do not all die or even get megacolon, so the allele will remain in populations regardless of whether it is dominant or recessive. Other breeders maintain that "low producers" (which would be mutants with low penetrance) are acceptable to continue breeding, but if such lines ever cross, they could have much higher penetrance, and to me, even low penetrance with only a single case of MC is not worth it. I believe breeders need to be very careful as to what they tell others about this issue (a lot of misconceptions are being spread) and need to be willing to sacrifice those markings for the health of lines. The megacolon effects will not just "go away" from the genes they are asociated with. As long as those alleles exist, there will be rats suffering and dying from the choices of breeders.

Please read some of the references on the bottom of this page for more information on megacolon. Only by informing breeders of the nature of this disease and development can we ever elliminate it from our lines. Also, you are welcome to look at my Power Point Presentation, which I created for a graduate course.

My Breedings

Because I never found any resources that explained the patterns I saw in my breedings, I recorded and deciphered my own lines. I have listed both the traditional "H" (self) allele and "h" (hooded) but have not ventured to guess what the other alleles are officially. They might be "He" and "hn" because I have not seen lethals or Irish markings.

  • Amiel, J. and S. Lyonnet 2001. Hirschsprung Disease, associated syndromes, and genetics: a review. J Med Genet vol. 38:729-739
  • Cantrell, A. S. et al. 2004. Interactions between Sox10 and EdnrB modulate penetrance and severity of aganglionosis in the Sox10Dom mouse model of Hirschsprung disease. Human Molecular Genetics vol. 13(19): 2289-2301
  • Herbarth, et al. 1998. Mutation of the Sry-related Sox10 gene in Dominant megacolon, a mouse model for human Hirschsprung disease. 1998. PNAS vol. 95, issue 9:5161-5165
  • McCallion, A.S. et al. 2003. Phenotype variation in two-locus mouse models of Hirschsprung disease: Tissue-specific interaction between Ret and Ednrb. PNAS vol. 100: 1826-1831
  • Young, H.M. et al. 2000. Embryology and development of the enteric nervous system. Gut vol. 47(Suppl 4):iv12-iv14.
  • http://www.hawthorn.org.uk/articles/genetics.html

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