| First Author | van De Sluis B | Year | 2002 |
| Journal | Hum Mol Genet | Volume | 11 |
| Issue | 2 | Pages | 165-73 |
| PubMed ID | 11809725 | Mgi Jnum | J:74624 |
| Mgi Id | MGI:2158883 | Doi | 10.1093/hmg/11.2.165 |
| Citation | van De Sluis B, et al. (2002) Identification of a new copper metabolism gene by positional cloning in a purebred dog population. Hum Mol Genet 11(2):165-73 |
| abstractText | Domesticated animal species such as dogs and cats, with their many different characteristics and breed-specific diseases, and their close relationship and shared environment with humans, are a potentially rich source for the identification of the genetic contribution to human biology and disease. Copper toxicosis in Bedlington terriers is a genetic disease occurring with a high prevalence worldwide and is unique to this breed. Copper homeostasis appears to be well regulated in mammals. Two copper carrier proteins have been identified in man and rodents which, when dysfunctional, cause either copper deficiency (Menkes disease) or copper accumulation in various tissues (Wilson disease). However, these proteins are not primarily involved in the biliary excretion of copper. Bedlington terriers have a high prevalence of copper toxicosis and it is well documented that their biliary excretion of copper is impaired. This disease is of direct relevance for the understanding of copper metabolism in mammals. Previously, we mapped the copper toxicosis gene to dog chromosome region 10q26. Based on DNA samples obtained from privately owned dogs, we were able to confine the localization of the copper toxicosis gene to a region of <500 kb by linkage disequilibrium mapping. While screening genes and expressed sequence tags in this region for mutations we found that exon 2 of the MURR1 gene is deleted in both alleles of all affected Bedlington terriers and in single alleles in obligate carriers. Although the function of the MURR1 gene is still unknown, the discovery of a mutated MURR1 gene in Bedlington terriers with copper toxicosis provides a new lead to disentangling the complexities of copper metabolism in mammals. |
