Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein
Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein
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DOI：
10.1016/s0168-8278(99)80172-x
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发表时间：
1999-07-01
影响因子：
25.7
通讯作者：
Lee, KK
中科院分区：
文献类型：
--
作者：
Yu, DY;Moon, HB;Lee, KK
背景/目标：慢性B型肝炎病毒感染是人类肝细胞癌的高危因素，HBV X蛋白作为一种多功能的病毒调节因子，在肝细胞癌的发生中起着积极的作用，这一点已被表达HBx的转基因小鼠肝细胞癌的高发病率所证实，尽管仍存在争议。本研究的目的是产生转基因小鼠表达的HBV X-基因下真实的启动子控制，并测试是否基因产物可以引起hepatic tumors.Methods：三个转基因小鼠系产生的X-基因构建到杂交（C57 BL/6xDBA）鸡蛋。通过蛋白质和mRNA分析测试基因表达。在18个月的观察期内，小鼠被处死，器官进行组织学examinations.Results：大体定义的肝细胞癌可重复地观察到在小鼠表达的X-蛋白，这是通过六代从11至18个月的年龄进行了调查。在14只11至18月龄的转基因小鼠中，发现12只患有肝细胞癌，肉眼或显微镜下。结论：本实验室生产的HBV X转基因小鼠中，除一例外，其它实验室生产的HBV X转基因小鼠均未发生肝肿瘤或其它病理现象，因此，本实验室生产的HBV X转基因小鼠的肝癌发生率（86%）可能是非常显著的。
Background/Aims: Chronic infection with hepatitis B virus is a high-risk factor for hepatocellular carcinoma in humans, The HBV X-protein, a multi-functional viral regulator, has been suspected to play a positive role in hepatocarcinogenesis, as demonstrated by the high incidence of hepatocellular carcinoma in HBx-expressing transgenic mice, although it is still controversial. The aim of this study was to generate transgenic mice expressing the HBV X-gene under authentic promoter control and to test whether the gene products can cause hepatic tumors.Methods: Three transgenic mouse lines were generated by microinjecting the X-gene construct into hybrid (C57BL/6xDBA) eggs. Gene expression was tested by protein and mRNA analyses. During an observation period of 18 months, mice were sacrificed and organs subjected to histologic examinations.Results: Grossly defined hepatocellular carcinomas reproducibly were observed in mice expressing the X-protein, which were investigated through six generations from the age of 11 to 18 months. Among 14 transgenic mice investigated from the age of 11 to 18 months, 12 were found to have hepatocellular carcinoma, grossly or microscopically. The lesion of the hepatocellular carcinoma disclosed a significant increase in the proliferating cell nuclear antigen in the nuclei,Conclusion: The incidence of hepatocellular carcinoma (86%) in our HBV X transgenic mice may be highly significant, since, except for one case, HBV X-gene transgenic mice produced in other laboratories did not develop liver tumor or any other pathologic phenomena.