Activity of a metallothionein-transthyretin fusion gene in transgenic mice. Possible effect of plasmid sequences on tissue-specific expression.

Three strains of transgenic mice carrying the mouse metallothionein-I (MT) promoter fused to the human transthyretin (TTR) structural gene plus pUC plasmid sequences were investigated for expression of the fusion gene. Human TTR was inducible in the serum of at least two strains and the fusion gene mRNA was detected in several tissues of all the strains. The testis showed constitutive mRNA synthesis, while the intestine and some other tissues showed inducible expression. Unexpectedly, however, the fusion gene activity was grossly suppressed in the liver and kidney of all the strains. Available data suggest that this suppression results from the presence of the plasmid sequences. Analysis of tissue DNAs shows that the methylation status of the promoter sequences varies from strain to strain, depending on their chromosomal position, and that some CpG sites in the proximal portion of the promoter are not methylated at all in the liver and kidney of two strains. These findings suggest that the plasmid sequences suppress the MT promoter activity in some specific tissues by a mechanism that does not involve DNA methylation.