Differential Expression of the Metallothionein Gene in Liver and Brain of Mice and Rats

Abstract

Expression of the metallothionein I (MT-I) gene was studied in liver and brain of control mice and rats, as well as following administration of Cd and lipopolysaccharide (LPS). Time-course studies revealed that MT mRNA reached a maximum in liver of both mice and rats 6 hr following treatment with Cd or LPS. MT mRNA from control and Cd- and LPS-treated rat brains could not be detected by Northern-blot analysis of total RNA, but Northern analysis with poly(A)-enriched RNA revealed that induction of MT mRNA in rat brain does occur with both Cd and LPS treatment. In contrast, mouse brain MT mRNA was easily detected by Northern-blot analysis of total RNA. It was also clear from Northern-blot analyses of both mouse and rat brain that LPS induced more MT .mRNA than did Cd. Quantitation of MT mRNA by solution hybridization revealed that Cd and [PS induced similar amounts of MT mRNA in livers of mice (about 0.64 fmol/μg total RNA by Cd and 0.68 by LPS) and rats (about 0.23 fmol/μg total RNA by Cd and 0.21 by LPS). Therefore, both inducers increased MT mRNA about threefold more in mouse liver than in rat liver. In mouse and rat brain, LPS induced about twice as much MT mRNA as did Cd (about 0.08 fmol/μg total RNA by Cd and 0.16 by LPS in mice and about 0.006 fmol/μg total RNA by Cd and 0.008 by LPS in rats). However, the actual amount of MT mRNA induced in rat brain by either inducer was minimal compared to that in mouse brain. In fact, Cd induced 13 times more MT mRNA in mouse brain than in rat brain, and LPS induced about 20 times more MT mRNA in mouse brain than in rat brain. Cd distribution to liver was similar in both mice and rats, but the Cd concentration in mouse brain was about 60% more than that in rat brain. Distribution of LPS was also similar in mouse and rat livers, as well as in mouse and rat brains. Therefore, there exists a difference in the expression of MT gene in both liver and brain of mice and rats, the expression in mice being higher than that in rats. These findings suggest that such differential expression of the MT gene cannot be entirely accounted for by the difference in the tissue distribution of inducers. Other tissue-specific and species-specific factors controlling MT gene expression appear to be involved.