Elevation of metallothionein gene expression associated with hepatic copper accumulation in Long-Evans Cinnamon mutant rat.

The mechanism of the metallothionein (MT) gene expression was investigated in a mutant rat, LEC, which exhibits an abnormal accumulation of copper in hepatocytes. The levels of MT mRNA were extremely high and correlated with the hepatic copper concentrations in LEC rat liver. Gel retardation assays in nuclear extracts from LEC rat liver showed an increase in the copper-dependent binding proteins, which bind to the metal responsive element (MRE) of the MT gene. These results suggest that the high intracellular copper accumulation results in the elevation of the MT gene expression through increasing a putative trans-activating factor in LEC rat.