TRANSGENIC MOUSE MODEL FOR STUDY OF VIRAL HEPATITIS C

虽然丙型肝炎病毒（HCV）是发病的主要原因， 尽管病毒性细胞病变效应在全世界范围内的死亡率中所起的作用仍然存在， 不清楚 研究丙型肝炎病毒结构蛋白的生物合成及其在丙型肝炎病毒感染中的作用。 致病作用，表达1b型HCV结构的转基因小鼠 蛋白质（核心，E1和E2）已构建使用肝脏特异性 发起人。在几个品系中检测到HCV转基因的表达 通过北方印迹，HCV特异性逆转录酶-聚合酶链 反应（RT-PCR）和Western免疫印迹。免疫组 分析显示核心蛋白主要存在于细胞质中 偶见细胞核染色，细胞质和细胞膜 E2蛋白在转基因肝脏中的表达。六个月后， 年龄，所有转基因谱系的肝脏保持组织学正常。 因此，HCV结构蛋白在此过程中不直接致细胞病变。 动物模型 我们的实验室也在培育转基因小鼠， 全长HCV基因组，并正在开发一个系统， 使用四环素诱导系统表达HCV转基因。 这些动物将提供一个有用的动物模型，不仅解决 HCV基因的免疫发病机制和致细胞病变潜能 产品，而且还研究HCV在体内的复制。

Although hepatitis C virus (HCV) is a leading cause of morbidity and mortality worldwide, the role of viral cytopathic effects remains unclear. To study the biosynthesis of HCV structural proteins and their pathogenic role, transgenic mice expressing type 1b HCV structural proteins (core, E1 and E2) have been constructed using liver-specific promoters. Expression of HCV transgenes was detected in several lines by Northern blot, HCV-specific reverse transcriptase-polymerase chain reaction (RT-PCR), and Western immunoblotting. Immunohistochemical analysis revealed a predominately cytoplasmic presence of core protein with occasional nuclear staining, and both cytoplasmic and membrane expression of the E2 protein in the transgenic livers. At six months of age, the livers of all transgenic lineages remain histologically normal. Therefore HCV structural proteins are not directly cytopathic in this animal model. Our laboratory are also generating transgenic mice with full-length HCV genome and are developing a system for inducible expression of HCV transgenes using the tetracycline-inducible system. These animal will provide a useful animal model not only to address issues of immunopathogenesis and cytopathic potential of HCV gene products but also to study HCV replication in vivo.