Correlation of Tissue‐specific Methylation with Gene Inactivity in Hepatitis B Virus Transgenic Mice

We produced transgenic mice using two constructs, HB‐GII and 1.2HB‐BS, of hepatitis B virus (HBV) DNA. The former has been designed to express mRNAs for HBV surface antigen (HBsAg), and the later to express all mRNAs of HBV. Several lines of the transgenic mice carrying each construct were examined for the tissue‐specificity and level of HBV DNA expression, and for the relationship between expression and methylation of the transgenes. Only one out of ten for HB‐GII and one out of eight for 1.2HB‐BS were high producers of viral antigens. In high producers, transgenes were expressed in the liver and the kidneys. But in low producers, transgenes were usually expressed only in the kidneys. There is a reciprocal relationship between the level of expression and the degree of methylation, that is, the higher the level of expression, the less the degree of methylation. We also observed that the expression of the integrated HBV‐DNA was repressed by methylation following its passage through the female germline in one line. Thus, in addition to transacting factors that can control the gene expression positively or negatively, this tissue‐specific methylation may also be involved in the regulation of HBV gene expression.