ABERRANT TISSUE-SPECIFIC EXPRESSION OF THE TRANSGENE IN TRANSGENIC MICE THAT CARRY THE HEPATITIS-B VIRUS GENOME DEFECTIVE IN THE X-GENE

The control mechanisms for the transgene expression in mice that carry the hepatitis B virus genome defective in the polymerase and X genes were analyzed. Ten lines of transgenic mouse were established, and in seven lines the surface and e antigens were detected in the serum. In transgenic mice from five lines examined, the transgene was markedly e xpressed in a broad spectrum of tissues including the kidney, heart, b rain, muscle and intestine, but only poorly in the liver. In the kidne y and heart the 3.5 kb and 2.1 kb mRNAs were expressed, whereas only t he 0.8 kb and 4.0 kb mRNAs were detected in the testis and brain, resp ectively, suggesting that each of the mRNAs was transcribed through a different control mechanism. The surface, e and core antigens accumula ted in the kidney and heart. DNA was hypomethylated at a region closel y downstream of the enhancer in the liver, kidney and heart, and a DNa se I hypersensitive site was detected upstream of the enhancer in thes e tissues. In the testis, however, the whole transgene was hypomethyla ted and the DNase I hypersensitive site was closer to the enhancer. Th ese differences may be relevant to the preferential expression of the 0.8 kb mRNA in the testis, but cannot explain the inefficiency of tran sgene expression in the liver. Our observations suggest that the X pro tein is required for efficient expression of the viral gene in the liv er but not in other tissues.