urinary copper elevation in a mouse model of wilsons disease is a regulated process to specifically decrease the hepatic copper load尿铜海拔威尔逊氏病的小鼠模型是一个管理过程,特别是减少肝铜负载.pdf

Urinary Copper Elevation in a Mouse Model of Wilson’s Disease Is a Regulated Process to Specifically Decrease the Hepatic Copper Load 1 2 3 1 1 Lawrence W. Gray , Fangyu Peng , Shannon A. Molloy , Venkata S. Pendyala , Abigael Muchenditsi , 4 5 3 1 Otto Muzik , Jaekwon Lee , Jack H. Kaplan , Svetlana Lutsenko * 1 Department of Physiology, Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America, 2 Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America, 3 Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, Illinois, United States of America, 4 Carman and Ann Adams Department of Pediatrics and Department of Radiology, Wayne State University, School of Medicine, Detroit, Michigan, United States of America, 5 Redox Biology Center, Department of Biochemistry, University of Nebraska, Lincoln, Nebraska, United States of America Abstract Body copper homeostasis is regulated by the liver, which removes excess copper via bile. In Wilson’s disease (WD), this function is disrupted due to inactivation of the copper transporter ATP7B resulting in hepatic copper overload. High urinary copper is a diagnostic feature of WD linked to liver malfunction; the mechanism behind urinary copper elevation is not fully understood. Using Positron Emission Tomography-Computed Tomography (PET-CT) imaging of live Atp7b 2/ 2 mice at different stages of disease, a longitudinal metal analysis, and characterization of copper-binding molecules, we show that urinary copper elevation is a specific regulatory process