期刊
SCIENCE
卷 318, 期 5855, 页码 1418-1423出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1147880
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资金
- NIDDK NIH HHS [R01 DK064265, R01 DK064265-08] Funding Source: Medline
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.
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