基因研究人员发现，一个控制狗毛色的基因出乎意料地编码一个属于过去只知道是与抵抗微生物有关的蛋白质家族的蛋白质。在大多数哺乳动物中，毛色由两个基因决定，一个是负责深色的黑皮素受体-1(Melanocortin 1 receptor)基因，另一个是负责浅色的鼠灰色(Agouti)基因。但是在狗身上，毛色还涉及到第三个基因。Sophie Candille和同事把该基因确定在狗DNA上被称为K位点的一个小区域内，该基因能解释大多数品种狗的黄、黑、或斑纹颜色的不同，随后的生物化学和小鼠实验也支持这个结果。这个与毛色有关的基因编码CDB103，该蛋白质是防御素(beta-defensin)的一个成员，防御素是一类涉及内在免疫的小蛋白质家族。防御素的这个超出免疫功能的新作用将引导研究人员发现防御素涉及的其它新功能。
原始出处:
Published Online October 18, 2007
Science DOI: 10.1126/science.1147880
Research Articles
Submitted on July 16, 2007
Accepted on October 3, 2007
A -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 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@stanford.edu
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 -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 -defensins, a protein family previously implicated in innate immunity, and identify an additional class of ligands for signaling through melanocortin receptors.
