{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:59:06Z","timestamp":1791179946935,"version":"4.1.0"},"reference-count":39,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5855","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2007,11,30]]},"abstract":"<jats:p>\n                    Genetic analysis of mammalian color variation has provided fundamental insight into human biology and disease. In most vertebrates, two key genes,\n                    <jats:italic>Agouti<\/jats:italic>\n                    and\n                    <jats:italic>Melanocortin 1 receptor<\/jats:italic>\n                    (\n                    <jats:italic>Mc1r<\/jats:italic>\n                    ), encode a ligand-receptor system that controls pigment type-switching, but in domestic dogs, a third gene is implicated, the\n                    <jats:italic>K<\/jats:italic>\n                    locus, whose genetic characteristics predict a previously unrecognized component of the melanocortin pathway. We identify the\n                    <jats:italic>K<\/jats:italic>\n                    locus as \u03b2-\n                    <jats:italic>defensin 103<\/jats:italic>\n                    (\n                    <jats:italic>CBD103<\/jats:italic>\n                    ) 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 \u03b2-defensins, a protein family previously implicated in innate immunity, and identify an additional class of ligands for signaling through melanocortin receptors.\n                  <\/jats:p>","DOI":"10.1126\/science.1147880","type":"journal-article","created":{"date-parts":[[2007,10,18]],"date-time":"2007-10-18T21:18:21Z","timestamp":1192742301000},"page":"1418-1423","source":"Crossref","is-referenced-by-count":310,"title":["A \u03b2-Defensin Mutation Causes Black Coat Color in Domestic Dogs"],"prefix":"10.1126","volume":"318","author":[{"given":"Sophie I.","family":"Candille","sequence":"first","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA."},{"name":"Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK."},{"name":"Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA."},{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Kaelin","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA."},{"name":"Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK."},{"name":"Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA."},{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce M.","family":"Cattanach","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA."},{"name":"Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK."},{"name":"Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA."},{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Yu","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA."},{"name":"Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK."},{"name":"Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA."},{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren A.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA."},{"name":"Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK."},{"name":"Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA."},{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A.","family":"Nix","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA."},{"name":"Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK."},{"name":"Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA."},{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Kerns","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA."},{"name":"Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK."},{"name":"Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA."},{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila M.","family":"Schmutz","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA."},{"name":"Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK."},{"name":"Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA."},{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn L.","family":"Millhauser","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA."},{"name":"Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK."},{"name":"Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA."},{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Barsh","sequence":"additional","affiliation":[{"name":"Departments of Genetics and Pediatrics, Stanford University, Stanford, CA, USA."},{"name":"Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire, OX11 ORD, UK."},{"name":"Departments of Chemistry and Biochemistry, University of California at Santa Cruz (UCSC), Santa Cruz, CA 95064, USA."},{"name":"Department of Animal and Poultry Science, University of Saskatchewan, Saskatoon S7N 5A8, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0749.2003.00067.x"},{"key":"e_1_3_2_3_2","first-page":"395","year":"2006","unstructured":"G. S. Barsh, in The Pigmentary System, J. J. Nordlund et al., Eds. (Blackwell, Oxford, 2006), pp. 395\u2013410.","journal-title":"The Pigmentary System"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)80820-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1325670"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90572-8"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.10.3223"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(05)80067-4"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.7.3.454"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.3.316"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb03197.x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0733"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jhered.a111784"},{"key":"e_1_3_2_14_2","unstructured":"C. C. Little The Inheritance of Coat Color in Dogs (Comstock Ithaca NY 1957)."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.107.074237"},{"key":"e_1_3_2_16_2","first-page":"19","year":"2005","unstructured":"J. Sampson, M. M. Binns, in The Dog and Its Genome, E. A. Ostrander, U. Giger, K. Lindblad-Toh, Eds. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 2005), pp. 19\u201330.","journal-title":"The Dog and Its Genome"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00104.2005"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1180"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5540-2"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s003350010005"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-004-2377-1"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04338"},{"key":"e_1_3_2_23_2","unstructured":"For further details see the Supporting Online Material."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.12.030"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008557200"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.77.10.5754"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-006-9031-7"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000180050010"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.6.3053-3060.2002"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1086\/378157"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2005.08.018"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5439.525"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737292"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075565"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb03172.x"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/12506"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0306931101"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2003.tb03181.x"},{"key":"e_1_3_2_39_2","unstructured":"Single-letter abbreviations for the amino acid residues are as follows: A Ala; C Cys; D Asp; E Glu; F Phe; G Gly; H His; I Ile; K Lys; L Leu; M Met; N Asn; P Pro; Q Gln; R Arg; S Ser; T Thr; V Val; W Trp; and Y Tyr."},{"key":"e_1_3_2_40_2","unstructured":"This work was supported by grants from NIH to G.S.B. and to G.L.M. and by a grant from the Donald E. and Delia B. Baxter Foundation to S.I.C. We thank H. Manuel for technical assistance; Y. Kobayashi and the Stanford Transgenic Facility for advice and help with transgenic experiments; D. Bennett for melan-a cells; Y.-K. Yang for providing the Mcr expression constructs; E. A. Ostrander for providing some of the samples; and the dog owners and breeders who generously submitted DNA samples."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1147880","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T03:40:48Z","timestamp":1704858048000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1147880"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,11,30]]},"references-count":39,"journal-issue":{"issue":"5855","published-print":{"date-parts":[[2007,11,30]]}},"alternative-id":["10.1126\/science.1147880"],"URL":"https:\/\/doi.org\/10.1126\/science.1147880","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1092762.559015","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1092762.554887","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1092762.547682","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1092762.554866","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1092762.554287","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,11,30]]}}}