A -defensin mutation causes black coat color in domestic dogs.
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.
Candille
Sophie I
SI
Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA.
Kaelin
Christopher B
CB
Cattanach
Bruce M
BM
Yu
Bin
B
Thompson
Darren A
DA
Nix
Matthew A
MA
Kerns
Julie A
JA
Schmutz
Sheila M
SM
Millhauser
Glenn L
GL
Barsh
Gregory S
GS
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*
D054366:Agouti Signaling Protein; D044102:Receptor, Melanocortin, Type 1; D023083:beta-Defensins