Differential expression of four linked sheep metallothionein genes

Regulation of the closely linked endogenous sheep MT-Ia, MT-Ib, MT-Ic and MT-II genes by heavy metals and dexamethasone was studied in cultured sheep fibroblasts. Only MT-II mRNA was detectable before addition of any inducer. Addition of copper, zinc or cadmium salts to the culture medium increased the level of each mRNA; however, the magnitude of this response varied greatly between the four metallothionein genes. Following induction, levels of MT-Ia mRNA were the highest, followed by MT-II and MT-Ic mRNAs. The MT-Ib mRNA was only present at low levels. Zinc and cadmium were found to be the most effective inducers of each gene. The maximal response of the sMT-Ia, Ib and II genes to copper was only 30% of zinc and cadmium. The sMT-Ic gene responded very weakly to copper, less than 5% of the levels achieved with zinc. Only the MT-II mRNA increased in response to dexamethasone. In the liver of sheep on normal diets, the levels of MT-Ia, Ic and II mRNAs were found to be unexpectedly high and comparable to induced levels in fibroblasts.