A -defensin mutation causes black coat color in domestic dogs

Science. 2007 Nov 30;318(5855):1418-23. doi: 10.1126/science.1147880. Epub 2007 Oct 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agouti Signaling Protein / genetics
  • Agouti Signaling Protein / metabolism
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chromosome Mapping
  • Dogs / genetics*
  • Dogs / metabolism
  • Female
  • Hair Color / genetics*
  • Haplotypes
  • Humans
  • Keratinocytes / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Mutation
  • Polymorphism, Genetic
  • Receptor, Melanocortin, Type 1 / metabolism*
  • Sequence Analysis, DNA
  • Sequence Deletion
  • Signal Transduction
  • Skin / metabolism
  • beta-Defensins / chemistry
  • beta-Defensins / genetics*
  • beta-Defensins / metabolism*


  • Agouti Signaling Protein
  • Receptor, Melanocortin, Type 1
  • beta-Defensins