TRANSGENIC MOUSE MODEL FOR STUDY OF HEPATITIS C

尽管丙型肝炎病毒(丙型肝炎病毒)是导致 世界范围内的发病率和死亡率，病毒基因的影响 在体内，感染细胞上的表达尚不清楚。此前，我们 丙型肝炎病毒转基因小鼠的构建 结构蛋白(CORE、E1和E2)的表达。 丙型肝炎病毒结构蛋白在这种动物中不是直接的细胞病变 模特。使用DNA免疫，我们能够诱导抗体 和抗丙型肝炎病毒结构蛋白的T细胞增殖反应 这些转基因动物。研究正在进行中，以确定 是否会引发细胞毒性T细胞反应或肝炎 使用这种方法。我们的实验室也在培育转基因生物 全长表达丙型肝炎病毒多蛋白的小鼠，并正在形成 丙型肝炎病毒转基因诱导性表达系统 四环素诱导系统。使用Lacz或SV40标记 作为一名转基因记者，我们的初步研究表明 严密调控的转基因表达可以在 肝脏。这些动物将提供一个有用的动物模型，不仅 解决免疫病理机制和细胞病变潜能的问题 丙型肝炎病毒基因产物还可以研究丙型肝炎病毒在体内的复制。

Although hepatitis C virus (HCV) is a leading cause of morbidity and mortality worldwide, the effects of viral gene expression on infected cells remain unclear in vivo. Previously, we reported the construction of transgenic mice expressing HCV structural proteins (core, E1 and E2) and showed that expression of HCV structural proteins is not directly cytopathic in this animal model. Using DNA immunization, we were able to induce antibody and T cell proliferative responses against HCV structural proteins in these transgenic animals. Studies are in progress to determine whether cytotoxic T cell response or hepatitis could be elicited using this approach. Our laboratory is also generating transgenic mice expressing HCV polyprotein full-length and are developing a system for inducible expression of HCV transgene using the tetracycline-inducible system. Using either the LacZ or SV40 Tag as a reporter transgene, our preliminary studies suggested that a tightly regulated transgene expression could be achieved in the liver. 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.