Wilson's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Wilson's Disease, including details on treatment, causes, symptoms, medication.

Developmental expression of Commd1 in the liver of the Jackson toxic milk mouse.

Roberts EA, Lau CH, da Silveira TR, Yang S

Genetics and Genome Biology Program, Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ont., Canada. eve.roberts@sickkids.ca

Wilson disease (WD) is due to mutations in ATP7B, which encodes an intracellular metal-transporting P-type ATPase. In WD holoceruloplasmin production and biliary excretion of copper are decreased, leading to copper overload, oxidative stress and apoptotic cell death. Other copper-binding proteins include COMMD1, which is inactive in the Bedlington terrier hereditary copper toxicosis, and XIAP, which regulates apoptosis. We examined developmental expression of Commd1 and Xiap in the Jackson toxic milk mouse (Atp7b(tx-J), G712D missense mutation in Atp7b). Expression of Commd1 mRNA appeared unchanged by PCR but real-time PCR demonstrated 3- to 4-fold increase over the first 6 months of life. Immunodetectable Xiap dropped over the first 8 months of life and was nearly undetectable from 6 months onward. Cytosolic NF-kappaB rose then dropped precipitously at 5-6 months. In tx-j mice hepatic copper accumulation leads to decreased Xiap, increased Commd1; these responses ultimately fail to prevent progressive apoptotic cell damage.

Published 17 October 2007 in Biochem Biophys Res Commun, 363(4): 921-5.
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