Animal Models for Wilson Disease

Abstract Wilson disease (WD) is a multisystem disorder that manifests primarily with hepatic and neurological symptoms due to copper toxicity in liver and brain. More than two decades after identification of the defective gene, ATP7B , the underlying mechanisms of copper toxicity and the striking phenotypic diversity remain far from understood. Animal models with defects in the Atp7b homolog have provided new insights into pathophysiology of WD. Several rodent models harboring Atp7b defects have been described, which include inbred mouse models [toxic milk [tx; tx-r] mouse, Jackson tx [tx-j] mouse], the Atp7b −/− (knockout) mouse, as well as the Long-Evans Cinnamon and LPP rats, all of which develop liver disease. Brain copper accumulation accompanied by neurologic involvement was observed in several of these animals; however, symptoms were less severe compared to humans. These models are valuable for exploration of copper metabolism, gene expression, and investigation of WD progression. To facilitate mandatory new research on novel drugs, gene, and cell therapy, animal models constitute an invaluable tool.