Altered zinc balance in the Atp7b^-/- mouse reveals a mechanism of copper toxicity in Wilson disease.

ABSTRACT: Wilson disease (WD) is an autosomal recessive disorder caused by mutation in the ATP7B gene that affects copper transport in the body. ATP7B mutation damages copper transporter function, ultimately resulting in excessive copper accumulation and subsequent toxicity in both the liver and brain. Mechanisms of copper toxicity, however, are not well defined. The Atp7b-/- mouse model is well-characterized and presents a hepatic phenotype consistent with WD. In this study, we found that the untreated Atp7b-/- mice accumulate approximately 2-fold excess hepatic zinc compared to the wild type. We used targeted transcriptomics and proteomics to analyze the molecular events associated with zinc and copper accumulation in the Atp7b-/- mouse liver. Altered gene expression of Zip5 and ZnT1 zinc transpor

SUBMITTER: Meacham KA 

PROVIDER: S-EPMC6310031 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature