Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

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
Prev | Table of Contents | Next

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Dissection of Genetic Factors Modulating Fetal Growth in Cattle Indicates a Substantial Role of the Non-SMC Condensin I Complex, Subunit G (NCAPG) Gene.
A. Eberlein, A. Takasuga, K. Setoguchi, R. Pfuhl, K. Flisikowski, R. Fries, N. Klopp, R. Furbass, R. Weikard, and C. Kuhn (2009)
Genetics 183, 951-964
   Abstract »    Full Text »    PDF »
Through the Looking Glass, Mechanistic Insights from Enantiomeric Human Defensins.
G. Wei, E. de Leeuw, M. Pazgier, W. Yuan, G. Zou, J. Wang, B. Ericksen, W.-Y. Lu, R. I. Lehrer, and W. Lu (2009)
J. Biol. Chem. 284, 29180-29192
   Abstract »    Full Text »    PDF »
Novel Partners of SPAG11B Isoform D in the Human Male Reproductive Tract.
Y. Radhakrishnan, K. G. Hamil, J.-a. Tan, G. Grossman, P. Petrusz, S. H. Hall, and F. S. French (2009)
Biol Reprod 81, 647-656
   Abstract »    Full Text »    PDF »
Molecular genetics of human pigmentation diversity.
R. A. Sturm (2009)
Hum. Mol. Genet. 18, R9-R17
   Abstract »    Full Text »    PDF »
Molecular and Evolutionary History of Melanism in North American Gray Wolves.
T. M. Anderson, B. M. vonHoldt, S. I. Candille, M. Musiani, C. Greco, D. R. Stahler, D. W. Smith, B. Padhukasahasram, E. Randi, J. A. Leonard, et al. (2009)
Science 323, 1339-1343
   Abstract »    Full Text »    PDF »
Mapping DNA structural variation in dogs.
W.-K. Chen, J. D. Swartz, L. J. Rush, and C. E. Alvarez (2009)
Genome Res. 19, 500-509
   Abstract »    Full Text »    PDF »
Allelic recombination between distinct genomic locations generates copy number diversity in human {beta}-defensins.
S. A. Bakar, E. J. Hollox, and J. A. L. Armour (2009)
PNAS 106, 853-858
   Abstract »    Full Text »    PDF »
Synthesis, Structure, and Activities of an Oral Mucosal {alpha}-Defensin from Rhesus Macaque.
S. Vasudevan, J. Yuan, G. Osapay, P. Tran, K. Tai, W. Liang, V. Kumar, M. E. Selsted, and M. J. Cocco (2008)
J. Biol. Chem. 283, 35869-35877
   Abstract »    Full Text »    PDF »
Defensins and the dynamic genome: What we can learn from structural variation at human chromosome band 8p23.1.
E. J. Hollox, J. C.K. Barber, A. J. Brookes, and J. A.L. Armour (2008)
Genome Res. 18, 1686-1697
   Abstract »    Full Text »    PDF »
Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences.
G. Diamond, N. Beckloff, and L.K. Ryan (2008)
Journal of Dental Research 87, 915-927
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)