A -defensin mutation causes black coat color in domestic dogs

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 im...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2007-11, Vol.318 (5855), p.1418-1423
Main Authors: 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
Format: Article
Language:English
Subjects:
Agouti Signaling Protein - genetics
Agouti Signaling Protein - metabolism
Amino Acid Sequence
Animals
beta-Defensins - chemistry
beta-Defensins - genetics
beta-Defensins - metabolism
Cell Line
Chromosome Mapping
Color
Dogs
Dogs - genetics
Dogs - metabolism
Female
Genetics
Hair Color - genetics
Haplotypes
Humans
Keratinocytes - metabolism
Male
Mice
Mice, Transgenic
Molecular Sequence Data
Mutation
Polymorphism, Genetic
Proteins
Receptor, Melanocortin, Type 1 - metabolism
Sequence Analysis, DNA
Sequence Deletion
Signal Transduction
Skin - metabolism
Transgenic animals
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Summary: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 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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1147880