Wilson's disease is an autosomal recessive disorder in which the liver does not properly release
copper into bile, resulting in prominent
copper accumulation in various tissues. Affected patients suffer from hepatic disorders and severe neurological defects. Experimental studies in mutant mice in which the
copper-transporting ATPase gene (Atp7b) is disrupted revealed a drastic, time-dependent accumulation of hepatic
copper that is accompanied by formation of regenerative nodes resembling
cirrhosis. Therefore, these mice represent an excellent exploratory model for
Wilson's disease. However, the precise time course in hepatic
copper accumulation and its impact on other trace metals within the liver is yet poorly understood. We have recently established novel
laser ablation inductively coupled plasma mass spectrometry protocols allowing quantitative
metal imaging in human and murine liver tissue with high sensitivity, spatial resolution, specificity and quantification ability. By use of these techniques, we here aimed to comparatively analyse hepatic
metal content in wild-type and Atp7b deficient mice during ageing. We demonstrate that the age-dependent accumulation of hepatic
copper is strictly associated with a simultaneous increase in
iron and
zinc, while the intrahepatic concentration and distribution of other metals or
metalloids is not affected. The same findings were obtained in well-defined human liver samples that were obtained from patients suffering from
Wilson's disease. We conclude that in
Wilson's disease the imbalances of hepatic
copper during ageing are closely correlated with alterations in intrahepatic
iron and
zinc content.