Atp7b-/- mice as a model for studies of Wilson's disease.

Abstract

Wilson's disease is a severe human disorder of copper homoeostasis. The disease is associated with various mutations in the ATP7B gene that encodes a copper-transporting ATPase, and a massive accumulation of copper in the liver and several other tissues. The most frequent disease manifestations include a wide spectrum of liver pathologies as well as neurological and psychiatric abnormalities. A combination of copper chelators and zinc therapy has been used to prevent disease progression; however, accurate and timely diagnosis of the disease remains challenging. Similarly, side effects of treatments are common. To understand better the biochemical and cellular basis of Wilson's disease, several animal models have been developed. This review focuses on genetically engineered Atp7b(-/-) mice and describes the properties of these knockout animals, insights into the disease progression generated using Atp7b(-/-) mice, as well as advantages and limitations of Atp7b(-/-) mice as an experimental model for Wilson's disease.