Phenotypic analysis of the HBx transgenic mice

• Main Authors: Bo-Kuan Wu, 吳柏寬
• Other Authors: Ting-Fen Tsai
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/44910385065180547353

碩士 === 國立陽明大學 === 遺傳學研究所 === 92 === The hepatitis B virus X protein (HBx) has been suggested to play a major role by clinical data and experimental evidences on HBV-induced hepatocellular carcinoma (HCC) development. However, the relationship of HBx and carcinogenesis remains controversial. In order to investigate the physiological effects of HBx, we generated four independent lines of transgenic mice expressing HBx driven by the liver-specific albumin promoter. The effect of HBx over-expression on regenerating liver was studied by two-thirds partial hepatectomy (PHx) strategy which provides an excellent in vivo model for studying hepatocyte cell cycle progression and proliferation. Low survival rate and decreased liver mass recovery of HBx transgenic mice was observed after PHx comparing with wild-type control. Our preliminary data indicated G1 arresting of cell cycle progression in the regenerating liver of the HBx transgenic mice based on analysis of (1) expression profile of cell cycle related genes, (2) BrdU incorporation of DNA synthesis, and (3) mitotic index of regenerating liver. In addition, prolonged mRNA expression of the immediate early genes, i.e. c-myc, c-fos, c-jun and junB, as well as abnormal cell death was detected in the regenerating liver of HBx transgenic mice post-hepatectomy. On the other hand, pathological analysis of the HBx transgenic liver indicated that hepatic steatosis was observed as early as 6 months of age. HCC was developed on 14-month-old transgenic liver with acinar and pseudoglandular histopathological characters of human HCC. The pathological effects of HBx are currently under investigation.