title: 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).
abstract: BACKGROUND
  In the domestic rabbit (Oryctolagus cuniculus), classical genetic studies have identified five alleles at the Extension locus: ED (dominant black), ES (steel, weaker version of ED), E (wild type, normal extension of black), eJ(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 ED or ES) and recessive red (c.304_333del30; allele e) coat colours. It remained to characterize the eJallele 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 (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.
  
  
  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.
authors.affiliation: DIPROVAL, Sezione di Allevamenti Zootecnici, University of Bologna, Via F,lli Rosselli 107, 42123 Reggio Emilia, Italy. luca.fontanesi@unibo.it
authors.forename: Luca
authors.initials: L
authors.lastname: Fontanesi
authors.forename: Emilio
authors.initials: E
authors.lastname: Scotti
authors.forename: Michela
authors.initials: M
authors.lastname: Colombo
authors.forename: Francesca
authors.initials: F
authors.lastname: Beretti
authors.forename: Lionel
authors.initials: L
authors.lastname: Forestier
authors.forename: Stefania
authors.initials: S
authors.lastname: Dall'Olio
authors.forename: Séverine
authors.initials: S
authors.lastname: Deretz
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Russo
authors.forename: Daniel
authors.initials: D
authors.lastname: Allain
authors.forename: Ahmad
authors.initials: A
authors.lastname: Oulmouden
mesh_terms: D054366:Agouti Signaling Protein / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D006200:Hair Color / Q000235:genetics*; D011817:Rabbits / Q000235:genetics*; D044102:Receptor, Melanocortin, Type 1 / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: D054366:Agouti Signaling Protein; D044102:Receptor, Melanocortin, Type 1