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Originally published in Science Express on 18 October 2007
Science 30 November 2007:
Vol. 318. no. 5855, pp. 1418 - 1423
DOI: 10.1126/science.1147880
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Research Articles

A β-Defensin Mutation Causes Black Coat Color in Domestic Dogs

Sophie I. Candille,1* Christopher B. Kaelin,1* Bruce M. Cattanach,2 Bin Yu,3 Darren A. Thompson,3 Matthew A. Nix,3 Julie A. Kerns,1{dagger} Sheila M. Schmutz,4 Glenn L. Millhauser,3 Gregory S. Barsh1{ddagger}

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.

1 Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA.
2 Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK.
3 Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA.
4 Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada.

* These authors contributed equally to the work.

{dagger} Present address: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

{ddagger} To whom correspondence should be addressed. E-mail: gbarsh{at}stanford.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Science. ISSN 0036-8075 (print), 1095-9203 (online)