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Published Online October 18, 2007
Science DOI: 10.1126/science.1147880

Research Articles

Submitted on July 16, 2007
Accepted on October 3, 2007

A {beta}-Defensin Mutation Causes Black Coat Color in Domestic Dogs

Sophie I. Candille 1{dagger}, Christopher B. Kaelin 1{dagger}, Bruce M. Cattanach 2, Bin Yu 3, Darren A. Thompson 3, Matthew A. Nix 3, Julie A. Kerns 4, Sheila M. Schmutz 5, Glenn L. Millhauser 3, Gregory S. Barsh 1*

1 Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA.
2 MRC Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK.
3 Departments of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
4 Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA; Present address: Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
5 Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada.

* To whom correspondence should be addressed.
Gregory S. Barsh , E-mail: gbarsh{at}stanford.edu

{dagger}These authors contributed equally to this work.

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 new component of the melanocortin pathway. Here 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.


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