title: A -defensin mutation causes black coat color in domestic dogs.
abstract: Genetic analysis of mammalian color variation has provided fundamental insight into human biology and disease. In most vertebrates, two key genes, Agouti and Melanocortin 1 receptor (Mc1r), encode a ligand-receptor system that controls pigment type-switching, but in domestic dogs, a third gene is implicated, the K locus, whose genetic characteristics predict a previously unrecognized component of the melanocortin pathway. We identify the K locus as beta-defensin 103 (CBD103) and show that its protein product binds with high affinity to the Mc1r and has a simple and strong effect on pigment type-switching in domestic dogs and transgenic mice. These results expand the functional role of beta-defensins, a protein family previously implicated in innate immunity, and identify an additional class of ligands for signaling through melanocortin receptors.
authors.affiliation: Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA.
authors.forename: Sophie I
authors.initials: SI
authors.lastname: Candille
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Kaelin
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cattanach
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.forename: Darren A
authors.initials: DA
authors.lastname: Thompson
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Nix
authors.forename: Julie A
authors.initials: JA
authors.lastname: Kerns
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Schmutz
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Millhauser
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Barsh
mesh_terms: D054366:Agouti Signaling Protein / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D004285:Dogs / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006200:Hair Color / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D044102:Receptor, Melanocortin, Type 1 / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism; D023083:beta-Defensins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D054366:Agouti Signaling Protein; D044102:Receptor, Melanocortin, Type 1; D023083:beta-Defensins