Corbee Ronald Jan, Penning Louis C
Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands.
Animals (Basel). 2021 Feb 25;11(3):601. doi: 10.3390/ani11030601.
Wilson's Disease is a rare autosomal recessive disorder in humans, often presenting with hepatic copper overload. Finding the genetic cause of a rare disease, especially if it is related to food constituents like the trace element copper, is a Herculean task. This review describes examples of how the unique population structure of in-bred dog strains led to the discovery of a novel gene and two modifier genes involved in inherited copper toxicosis. COMMD1, after the discovery in 2002, was shown to be a highly promiscuous protein involved in copper transport, protein trafficking/degradation, regulation of virus replication, and inflammation. Mutations in the ATP7A and ATP7B proteins in Labrador retrievers and Dobermann dogs resulted in a wide variation in hepatic copper levels in these breeds. To our knowledge, numerous dog breeds with inherited copper toxicosis of unknown genetic origin exist. Therefore, the possibility that men's best friend will provide new leads in rare copper storage diseases seems realistic.
威尔逊氏病是一种人类罕见的常染色体隐性疾病，常表现为肝脏铜过载。找到一种罕见疾病的遗传病因，尤其是如果它与食物成分（如微量元素铜）有关，是一项艰巨的任务。这篇综述描述了近亲繁殖犬种独特的种群结构如何导致发现一个新基因和两个参与遗传性铜中毒的修饰基因的实例。2002年发现的COMMD1被证明是一种高度混杂的蛋白质，参与铜运输、蛋白质运输/降解、病毒复制调节和炎症。拉布拉多猎犬和杜宾犬中ATP7A和ATP7B蛋白的突变导致这些品种肝脏铜水平存在广泛差异。据我们所知，存在许多遗传起源不明的遗传性铜中毒犬种。因此，人类最好的朋友（狗）将为罕见的铜储存疾病提供新线索的可能性似乎是现实的。
