OMIA 001199-9986 : Coat colour, extension in Oryctolagus cuniculus

In other species: cattle , dog , horse , red fox , pig , sheep , jaguar , jaguarundi , American black bear , woolly mammoth , domestic cat , domestic guinea pig , goat , Arctic fox , rock pocket mouse , oldfield mouse , gray squirrel , lesser earless lizard , little striped whiptail , water buffalo , domestic yak , alpaca , , coyote , reindeer , Geoffroy's cat , Colocolo , ass , Arabian camel , Mongolian gerbil , raccoon dog , fallow deer , zebu

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 266300 , 155555 , 203200

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal

Considered a defect: no

Key variant known: yes

Year key variant first reported: 2006

Cross-species summary: The extension locus encodes the melanocyte-stimulating hormone receptor (MSHR; now known as MC1R). This receptor controls the level of tyrosinase within melanocytes. Tyrosinase is the limiting enzyme involved in synthesis of melanins: high levels of tyrosinase result in the production of eumelanin (dark colour, e.g. brown or black), while low levels result in the production of phaeomelanin (light colour, e.g. red or yellow). When melanocyte-stimulating hormone (MSH) binds to its receptor, the level of tyrosinase is increased, leading to production of eumelanin. The wild-type allele at the extension locus corresponds to a functional MSHR, and hence to dark pigmentation in the presence of MSH. As explained by Schneider et al. (PLoS Genet 10(2): e1004892; 2015), "The most common causes of melanism (black coat) mutations are gain-of-function alterations in MC1R, or loss-of function alterations in ASIP, which encodes Agouti signaling protein, a paracrine signaling molecule that inhibits MC1R signaling". Mutations in MC1R have been associated with white colouring in several species.

Species-specific description: See Robinson (1958, pp. 248-251)

Molecular basis: Fontanesi et al. (2006) reported that the recessive (red) e allele is "a 30-nucleotide in-frame deletion (c.304_333del30)"; and "a 6-nucleotide in-frame deletion (c.280_285del6) . . . may be allele E(D) or allele E(S) [dominant black]".

Fontanesi et al. (2010) showed that allele eJ (Extension Japanese allele) is determined by a 6 bp in-frame deletion flanked by a G>A transition in 5' (c.124G>A;125_130del6) in the MC1R gene. In homozygous eJ/eJ rabbits, this allele is expressed in skin areas with black hair, whereas it is not expressed in skin with red hair areas (Fontanesi et al., 2010). [Based on wording provided by Luca Fontanesi to FN]

By using the CRISPR/Cas9 system, Xiao et al. (2019) bred rabbits with a light yellow coat colour by creating deletions in the MC1R gene. These rabbits are genetically-modified organiams (GMO).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MC1R melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) Oryctolagus cuniculus - no genomic information (-..-) MC1R Homologene, Ensembl, NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Dominant black or Steel MC1R E(D) or E(S) deletion, small (<=20) c.124G>A;125_130del6 2006 16978179
Red/fawn/yellow MC1R e deletion, gross (>20) c.304_333del30 2006 16978179
Japanese brindling MC1R eJ complex rearrangement c.[124G>A;125_130del6] "6 bp-in frame deletion flanked by a G > A transition in 5' (c.[124G>A;125_130del6]) that was present in all animals with Japanese brindling coat colour and pattern." (Fontanesi et al., 2010) 2010 20594318


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2021 Jia, X., Ding, P., Chen, S., Zhao, S., Wang, J., Lai, S. :
Analysis of <i>MC1R, MITF, TYR, TYRP1</i>, and <i>MLPH</i> Genes Polymorphism in Four Rabbit Breeds with Different Coat Colors. Animals (Basel) 11:, 2021. Pubmed reference: 33466315. DOI: 10.3390/ani11010081.
2019 Xiao, N., Li, H., Shafique, L., Zhao, S., Su, X., Zhang, Y., Cui, K., Liu, Q., Shi, D. :
A Novel Pale-Yellow Coat Color of Rabbits Generated <i>via</i><i>MC1R</i> Mutation With CRISPR/Cas9 System. Front Genet 10:875, 2019. Pubmed reference: 31620174. DOI: 10.3389/fgene.2019.00875.
2010 Fontanesi, L., Scotti, E., Colombo, M., Beretti, F., Forestier, L., Dall'Olio, S., Deretz, S., Russo, V., Allen, D., Oulmouden, A. :
A composite six bp in-frame deletion in the melanocortin 1 receptor (MC1R) gene is associated with the Japanese brindling coat colour in rabbits (Oryctolagus cuniculus). BMC Genet 11:59, 2010. Pubmed reference: 20594318. DOI: 10.1186/1471-2156-11-59.
2007 Fontanesi, L., Tazzoli, M., Russo, V. :
Non-invasive and simple methods for sampling DNA for PCR analysis of melanocortin 1 receptor (MC1R) gene mutations: a technical note. World Rabbit Science 15:121-126, 2007.
2006 Fontanesi, L., Tazzoli, M., Beretti, F., Russo, V. :
Mutations in the melanocortin 1 receptor (MC1R) gene are associated with coat colours in the domestic rabbit (Oryctolagus cuniculus). Anim Genet 37:489-93, 2006. Pubmed reference: 16978179. DOI: 10.1111/j.1365-2052.2006.01494.x.
1958 Robinson, R. :
Genetic studies of the rabbit. Bibliographia Genetica 17:229–558, 1958.
1924 Castle, W.E. :
Genetics of the Japanese rabbit Journal of Genetics 14:225-229, 1924.
Punnett, RC. :
On the "Japanese" rabbit Journal of Genetics 14:230-240, 1924.

Edit History

  • Created by Frank Nicholas on 13 Jul 2009
  • Changed by Frank Nicholas on 08 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 17 Jun 2013
  • Changed by Frank Nicholas on 31 Dec 2013
  • Changed by Frank Nicholas on 29 Apr 2016
  • Changed by Frank Nicholas on 14 Feb 2020