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)

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 (eJ) was present in homozygous state in Japanese, Rhinelander and Dutch tricolour rabbits only (except one albino rabbit). Rabbits with eJ/eJ genotype were non fixed at the non-agouti mutation we previously identified in the ASIP gene. Segregation in F1 and F2 families confirmed the order of dominance already determined by classical genetic experiments with a possible dose effect evident comparing eJ/eJ and eJ/e animals. MC1R mRNA was expressed in black hair skin regions only.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.Coat colour in mammals is determined by the presence, distribution and biochemical activity of the melanocytes, which are specialized cells where eumelanins (black/brown pigments) and pheomelanins (yellow/red pigments) are synthesized. More than 300 loci have been shown to affect coat colour in mice regulating or altering melanocyte development and migration during embryogenesis, melanocyte morphology and functions, its components and its enzymatic machinery [1,2]. However, Extension and Agouti are