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The agouti locus encodes the agouti signalling protein (ASIP) which is involved in determining the switch from eumelanin to pheomelanin synthesis in melanocytes. In the domestic rabbit (Oryctolagus cuniculus) early studies indicated three alleles at this locus: A, light-bellied agouti (wild type); at, black and tan; a, black nonagouti. We characterized the rabbit ASIP gene and identified the causative mutation (an insertion in exon 2) of the black nonagouti allele whose frequency was evaluated in 31 breeds. Phylogenetic analysis of ASIP sequences from Oryctolagus and 9 other species of the family Leporidae placed Oryctolagus as sister species to Pentalagus and Bunolagus. Transcription analysis in wild type agouti rabbits revealed the presence of two major transcripts with different 5′-untranslated regions having ventral or dorsal skin specific expression. ASIP gene transcripts were also detected in all examined rabbit tissues distinguishing the rabbit expression pattern from what was observed in wild type mice.

Pigmentation in mammals is mainly determined by the distribution of pheomelanin and eumelanin pigments which produce red/yellow and dark phenotypes, respectively. The relative amount of eumelanin and phaeomelanin in the melanocytes is controlled primarily by two loci, the Extension and Agouti loci. Extension locus encodes the melanocortin 1 receptor (MC1R). MC1R mutations have been identified to alter coat colour and pigment synthesis in several mammals. Analysing almost the complete coding region of the Oryctolagus cuniculus MC1R gene, we recently identified two mutations associated with red (recessive allele e of the Extension locus) or black (ED or ES, dominant black or steel, weaker version of ED) coat colours in different European rabbit breeds. Here we completed the sequence of the 953 bp coding region of the MC1R gene in O. cuniculus excluding the presence of additional common disrupting or functional mutations. Agouti locus encodes for the agouti signalling protein (ASIP). In European rabbit, classical studies have suggested the presence of three alleles at the Agouti locus: A (wild type allele), at (black and tan) and a (non-agouti). We sequenced the O. cuniculus ASIP exon 2 region and identified three mutations. Two were synonymous substitutions and one was an insertion of 1 bp. This insertion causes a frameshift of the translation suggesting that this mutation might be the molecular basis of the recessive black non-agouti allele at the Agouti locus (a allele). Genotyping this mutation in a larger number of animals confirmed the fixation of the insertion in all animals of breeds with black/dark coat colour. In addition, MC1R gene and ASIP exon 2 were sequenced in other Leporid species obtaining useful information to study these two coat colour genes from an evolutionary point of view.