Araki K, Akagi K, Miyazaki J, Matsubara K, Yamamura K
Institute for Medical Genetics, Kumamoto University Medical School.
Jpn J Cancer Res. 1990 Dec;81(12):1265-71. doi: 10.1111/j.1349-7006.1990.tb02689.x.
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.
我们使用乙型肝炎病毒（HBV）DNA的两种构建体HB - GII和1.2HB - BS培育了转基因小鼠。前者被设计用于表达HBV表面抗原（HBsAg）的mRNA，后者用于表达HBV的所有mRNA。对携带每种构建体的几系转基因小鼠进行了HBV DNA表达的组织特异性和水平以及转基因表达与甲基化之间关系的检测。HB - GII的十系中有一系、1.2HB - BS的八系中有一系是病毒抗原的高产系。在高产系中，转基因在肝脏和肾脏中表达。但在低产系中，转基因通常仅在肾脏中表达。表达水平与甲基化程度之间存在反比关系，即表达水平越高，甲基化程度越低。我们还观察到，在一个品系中，整合的HBV - DNA在通过雌性生殖系后，其表达受到甲基化的抑制。因此，除了可正向或负向控制基因表达的反式作用因子外，这种组织特异性甲基化可能也参与了HBV基因表达的调控。
