RT Journal Article SR Electronic T1 A β-Defensin Mutation Causes Black Coat Color in Domestic Dogs JF Science JO Science FD American Association for the Advancement of Science SP 1418 OP 1423 DO 10.1126/science.1147880 VO 318 IS 5855 A1 Candille, Sophie I. A1 Kaelin, Christopher B. A1 Cattanach, Bruce M. A1 Yu, Bin A1 Thompson, Darren A. A1 Nix, Matthew A. A1 Kerns, Julie A. A1 Schmutz, Sheila M. A1 Millhauser, Glenn L. A1 Barsh, Gregory S. YR 2007 UL http://science.sciencemag.org/content/318/5855/1418.abstract AB 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 β-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 β-defensins, a protein family previously implicated in innate immunity, and identify an additional class of ligands for signaling through melanocortin receptors.