title: Canine Models for Copper Homeostasis Disorders.
abstract: Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted.
authors: Department of Clinical Sciences of Companion animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands. x.wu@uu.nl.
authors: Xiaoyan
authors: X
authors: Wu
authors: Department of Clinical Sciences of Companion animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands. P.A.J.Leegwater@uu.nl.
authors: Peter A J
authors: PA
authors: Leegwater
authors: Department of Clinical Sciences of Companion animals, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 108, 3584 CM Utrecht, The Netherlands. H.Fieten@uu.nl.
authors: Hille
authors: H
authors: Fieten
mesh_terms: D000818:Animals; D015913:Chelation Therapy; D002874:Chromosome Mapping; D003300:Copper / Q000378:metabolism*; D004035:Diet Therapy; D004195:Disease Models, Animal; D004285:Dogs; D056726:Genetic Association Studies; D006527:Hepatolenticular Degeneration / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D006706:Homeostasis; D006801:Humans; D008664:Metal Metabolism, Inborn Errors / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D016377:Organ Transplantation
chemical_list: D003300:Copper
keywords: ATP7A; ATP7B; Bedlington terrier; COMMD1; Labrador retriever; Menkes disease; Wilson disease; copper toxicosis; genetics; nutrition