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.