A gene that MisterMiceGuy is working with is the Roan gene. In order to learn more about this gene an inquiry was made to the Fancy Mouse Breeders’ Association private group that revealed there may not be much research that has been conducted into the Roan gene and that much of what is written is just conjecture (Sampson 2020). Additional comments indicated that laboratories may call the gene roan unstable (roun) and that there are two versions of the recessive Roan gene (Laigaie 2020, Wyss 2019).
The Roan mice currently circulating in the Fancy Mouse Hobby were initially found in a feeder colony owned by Jack Ball of San Jose, CA and was developed by him in the 1980s (Robbins 2014, Emerson 2020b). In 2009 descendants of Ball’s Roan mice were sent by Mike Choido of New York to Dr. Roland Fischer in Germany. It’s reported that all Roan mice in Europe come from this line of mice (Robbins 2014). When it was first discovered the gene was referred to as “Jack Ball Roan” (Emerson 2020a).
According to Ball (1986) most genetic textbooks list the roan gene as lethal. The exact text books are not listed and MisterMiceGuy was unable to locate them. Lethal in this context seems to mean that homozygotes will fail to be born or will die shortly after birth (Ball 1986). The Roan gene that MisterMiceGuy is recessive and does not appear to be a lethal gene. This may indicate that there are multiple roan-like genes in circulation.
A literature search on Google Scholar and Medline for Roan Mice, Unstable Roan Mice, and Merle mice only returns one article by De Sepulveda, Guenet, and Panthier (1995) that discusses a “roan effect” gene (Wrio). This gene appears to be dominant and occured spontaneously in an inbred strain maintained at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil. Interestingly this gene is both dominant and lethal in its homozygous state which is similar to the gene in textbooks described by Ball (1986). Unfortunately, this gene is not the gene that MisterMiceGuy is working with because it is dominant. Although it is not the same, it does have a similar appearance and it is possible that this gene functions similarly to the recessive gene that is in MisterMiceGuy’s possession.
Confusingly, in addition to reports of there being two recessive roan genes (discussed later) there are also reports that both genes have variable expression. In some instances a roan mouse will have a coat that has a base color with white furs even distributed covering its entire body (see example 1). In other instances the mouse will have a different phenotype consisting of roan fur and solid patches (see example 2). This phenotypic variant is called Merle (Pochmann 1988). The solid patches are called “phenotypic reversions” because the coat is reverting back to its non-roan state (De Sepulveda, Guenet, and Panthier 1995). Animals with this phenotype are also known as mosaics (Pochmann 1988) but the mosaic term does not seem to be in common use in the fancy mouse community. Both versions of the recessive gene have this variable phenotype.
These solid patches are not symmetrical (De Sepulveda, Guenet, and Panthier 1995) and generally start and end at the midline (Pochmann 1988). They also seem randomly positioned (De Sepulveda, Guenet, and Panthier 1995) and not traditionally heritable (Pochmann 1988). Both Pachmann (1988) and De Sepulveda, Guenet, and Panthier (1995) compared the expression of the Roan gene to that of the pink-eyed unstable (pun) gene.
In the case of unstable genes such as pun, or potentially the recessive roan genes, the DNA is damaged in during the migration of cells during embryonic development. The DNA is only altered in certain cells through processes like hemizygous deletion or mitotic recombination (De Sepulveda, Guenet, and Panthier 1995). It was hypothesised by Pochmann (1988) that in the case of recessive Roan one of the alleles is lost randomly as the DNA is replicated and cells migrate from the midline across the embryo. The loss occurs at random leaving certain cells in a heterozygous state (a non-roan state) allowing pigment to be produced but only in select areas. This would explain why the pattern of solid patches in roan mice are not heritable and random.
Additional searches reveal that there are a variety of genes that produce white hairs in the coat such as Flecked (Fk), Freckled (Fkl), dominant roan (Rn), Varitint-Waddler (Va), Silver (si), and Misty (m) (Pochmann 1988 & Sviderskaya, Novak, Swank, and Bennett 1998). Based on photos and descriptions none of these are the same as the recessive Roan gene that is circulating in the American mouse breeding hobby today.
There have been reported to be two apparently distinct recessive Roan genes with similar phenotypic expression reported by Fancy Mouse Breeders. One has been identified as type 1 (early type) and the other is type 2 (late type) (Ball 1986, Wyss 2019). However, both variants seem to come from the single spontaneous mutation discovered by Ball in the 1980s (Emerson 2020b). If the gene developed as a spontaneous mutation in Ball’s colony it would seem highly unlikely that he would have had two instances of spontaneous mutation resulting in two genes with similar phenotype. MisterMiceGuy suspects that all of the phenotypic variants of the recessive roan gene (early, late, Roan, and Merle) come from the variable expression of a single gene.
The early type is described has having the roan pattern in place when the coat first comes in. It is distinguishable from late type because the white hairs will already be mixed in to certain patches of fur when the first coat develops and the animal will not change significantly as it ages (Ball 1988). This early type Roan development matches the hypothesis that Roan development has a similar mechanism to Pink-eye unstable pun as explained by Pochmann (1988). MisterMiceGuy has noticed that although his mice have been identified as the early type (Wyss 2019) it seems that the mice are born with mostly regular pigmentation and that the Roan pattern develops quickly after the coat grows in. This suggests that the Roan allele is not lost randomly during cell migration in the embryo. Perhaps what is randomly altered during embryonic cell migration is some sort of genetic factor that affects both A. if a cell will loose pigment and B. when a cell will loose pigment.
The late type as you might expect has poorly defined areas of roan and solid coloring when the coat first comes in. By the time the mouse is four or five weeks the coat rapidly fades to a lighter roan pattern revealing distinct solid patches in certain areas (Ball 1988). Being that in late type Roan the cells have pigment early on and then lose it suggests that the DNA is not lost during during cell replication during development and migration. It would seem that these cells maintain their homozygous state through embryonic development and then at some point later the DNA or melanocytes are lost. This supports MisterMiceGuy’s hypothesis that both early and late type recessive roan are the same gene and that there are additional modifiers affecting if a cell will lose pigmentation and when the pigmentation will be lost.
Additionally, MisterMiceGuy suspects that the Recessive Roan gene may be located at the W-locus on chromosome 5 and not a hypothetical “Ro” locus as is seemingly suggested on the Fancy Mouse Breeder groups and websites (Bernstein et al. 1990, Laigaie 2020, The Finnish Mouse Club 2020).
This is hypothesis is supported by the idea that W-locus genes are known to affect cell differentiation and coat color changes. Of particular interest is that the W-locus is known to have genes that produce pleiotropic developmental defects (Bernstein et al. 1990). Pleiotropic means that a single gene is responsible for a variety of phenotypes (Sheil 2020) which seems to be what we are observing in the Recessive Roan gene (Ball 1986, Pochmann 1988).
Similar effects can be seen on other W-locus genes whose phenotypes exhibit random and asymmetrical patterns such as the “Roan Effect” mice from Rio or Dominant white spotting W-locus mice (De Sepulveda, Guenet, & Panthier 1995, Geissler,McFarland, Russel, 1981).
Despite having complex and unknown genetic origins the Roan gene produces variable and stunning mice that are valuable contributions to the mouse breeding hobby. Additionally the roan gene can combine with many of the other coat color dilution genes such as black, chocolate, red, or even chinchilla to produce surprisingly beautiful mice (Ball 1986).
Updated March 25, 2020
References
Pochmann, V. (1988) Explanation of Roan Mouse Inheritance Factors. American Fancy Rat and Mouse Association. Retrieved from: https://www.afrma.org/roanmiceinh.htm?fbclid=IwAR36Ida8GpNQQGn0lHcafavg1MDkhT29BwbzZJlMsUjpPutYCWDFCJkGMBI
Ball, J. (1986) Breeding Roan Mice. American Fancy Rat and Mouse Association. Retrieved from: https://www.afrma.org/roanmice.htm
Geissler, E., McFarland, E., Russel, E. (1981) Analysis of pleiotropism at the dominant white spotting 
locus of the house mouse: a description of ten new W alleles. Genetics, 97, 337-361.
De Sepulveda, P., Guenet, J. L., & Panthier, J. J. (1995). Phenotypic reversions at the W/Kit locus mediated by mitotic recombination in mice. Molecular and Cellular Biology, 15(11), 5898–5905.
Laigaie, M. (2020, March 19) Merle is ro^un (roan unstable). retrieved from: https://www.facebook.com/groups/mousebreeders/?multi_permalinks=1350454325157523¬if_id=1584629546420063¬if_t=feedback_reaction_generic [Facebook update]
Sampson, K. (2020, March 19) Most is just theories. retrieved from: https://www.facebook.com/groups/mousebreeders/?multi_permalinks=1350454325157523¬if_id=1584629546420063¬if_t=feedback_reaction_generic [Facebook update]
Wyss, J. (2019, December 11) There are two versions. Early and late. You have early. Personal Facebook Message.
Sviderskaya, E. V., Novak, E. K., Swank, R. T., & Bennett, D. C. (1998). The murine misty mutation: phenotypic effects on melanocytes, platelets and brown fat. Genetics, 148(1), 381–390.
Robbin, K. (2014) Mouse Genetic Questions. American Fancy Rat and Mouse Association. retrieved from https://www.afrma.org/roanmice.htm
The Finnish Mouse Club (2020) Varieties. Retrieved from: http://www.hiiret.fi/eng/breeding/?pg=4&sub=11&ala=8
Bernstein, A., Chabot, B., Dubreuil, P., Reith, A., Nocka, K., Majumder, S., Ray, P., Besmer, P. (1990). The mouse W/c-kit locus. Ciba Foundation symposium, 148, 158-66.
Shiel, W. (2020) Medical Definition of Pleiotropic. MedicineNet. Retrieved from: https://www.medicinenet.com/script/main/art.asp?articlekey=4942
Emerson, M (2020a) We called it Jack ball roan. Facebook post retrieved from: https://www.facebook.com/groups/mousebreeders/1355472471322375/?comment_id=1355493717986917&reply_comment_id=1355498774653078¬if_id=1585151197268579¬if_t=group_comment_mention
Emerson, M (2020b) “Both are from him and descended from the original female he pulled out of his feeder colony.” Personal Facebook message.
Ryan David Tuttle, MA 