Metallothionein-null mice express altered genes during development

Metallothionein (MT) can modulate transcriptional activity in vitro. We exa mined whether the absence of MT affects gene expression in vivo. We compare d the hepatic RNA profiles of wild-type and MT-null neonatal mice using imp roved differential display. The hepatic MT level was maximal during neonata l development. We identified five cDNA fragments that were expressed in MT- null mice at different levels from those in wild-type mice. Two were fragme nts of MT-I and mutant MT-I cDNA. The sequences of the other cDNA fragments were identical to those of contrapsin, transketolase, and vanin-3. The lat ter two were upregulated, whereas contrapsin was down-regulated in neonatal MT-null mice. These mRNA levels were remarkably different between the two strains of neonatal mice. Further characterization of the regulated mRNA id entified here will determine whether or not they are primary or secondary e ffects of an MT deficiency. (C) 2000 Academic Press.