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Background  In the domestic rabbit ( Oryctolagus cuniculus ), classical genetic studies have identified five alleles at the  Extension  locus:  E   D   (dominant black),  E   S   (steel, weaker version of  E   D  ),  E  (wild type, normal extension of black),  e   J  (Japanese brindling, mosaic distribution of black and yellow) and  e  (non-extension of black, yellow/red with white belly). Sequencing almost the complete coding sequence (CDS) of the rabbit  MC1R  gene, we recently identified two in-frame deletions associated with dominant black (c.280_285del6; alleles  E   D   or  E   S  ) and recessive red (c.304_333del30; allele  e ) coat colours. It remained to characterize the  e   J  allele whose phenotypic effect is similar to the  Orange  and  Sex-linked yellow  loci of cat and Syrian hamster.    Results  We sequenced the whole CDS in 25 rabbits of different coat colours including 10 Japanese and 10 Rhinelander (tricolour) rabbits and identified another 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. These mutations eliminate two amino acids in the first transmembrane domain and, in addition, cause an amino acid substitution at position 44 of the wild type sequence. Genotyping 371 rabbits of 31 breeds with different coat colour this allele ( e   J  ) was present in homozygous state in Japanese, Rhinelander and Dutch tricolour rabbits only (except one albino rabbit). Rabbits with  e   J  / e   J   genotype were non fixed at the non-agouti mutation we previously identified in the  ASIP  gene. Segregation in F 1  and F 2  families confirmed the order of dominance already determined by classical genetic experiments with a possible dose effect evident comparing  e   J  / e   J   and  e   J  / e  animals.  MC1R  mRNA was expressed in black hair skin regions only.    Conclusions  The c.[124A;125_130del6] allele may be responsible for a MC1R variant determining eumelanin production in the black areas. However, the mechanism determining the presence of both red and black hairs in the same animal seems more complex. Expression analyses of the c.[124A;125_130del6] allele suggest that  MC1R  transcription may be regulated epigenetically in rabbits with the Japanese brindling phenotype. Further studies are needed to clarify this issue.

bmc genomic data

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)