Methylation of Hepatitis B Virus DNA and Liver-specific Suppression of RNA Production in Transgenic Mouse

Three lines of transgenic mice carrying hepatitis B virus (HBV) DNA were produced. In a pSHBIBB transgenic mouse carrying one copy of BamHl fragment of HBV with a deletion of BgHl-BgtLI fragment, no RNA transcription was observed. Transgenic mice that had integrated either one or three tandem copies of HBV DNA produced RNA in various tissues except liver. However, neither initiation nor termination of transcription occurred at the correct place. Hepatitis B surface antigen and hepatitis B e antigen were not detectable in these transgenic mice. HBV DNA was methylated at all CCGG sequences, which might have resulted in aberrant RNA production. In two out of five transgenic mice HBV DNA was integrated into the Y chromosome. Although the frequency is unusually high, the mechanism is not known yet.