A β-Defensin Mutation Causes Black Coat Color in Domestic Dogs
2007
Candille, Sophie I. | Kaelin, Christopher B. | Cattanach, Bruce M. | Yu, Bin | Thompson, Darren A. | Nix, Matthew A. | Kerns, Julie A. | Schmutz, Sheila M. | Millhauser, Glenn L. | Barsh, Gregory S.
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.
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