TRANSGENIC MOUSE MODEL FOR STUDY OF HEPATITIS C

用于研究丙型肝炎的转基因小鼠模型

• 批准号: 6105876
• 负责人: T. Jake Liang
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6105876
• 关键词: disease /disorder model; gene expression; gene induction /repression; genetic promoter element; genetically modified animals; hepatitis C; hepatitis C virus; immunocytochemistry; laboratory mouse; liver; model design /development; northern blottings; polymerase chain reaction; protein biosynthesis; virus cytopathogenic effect; virus protein; virus replication; western blottings

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.

尽管丙型肝炎病毒（HCV）是主要原因 世界范围内发病率和死亡率，病毒基因的影响 在体内感染细胞上的表达仍不清楚。此前我们 报道了表达HCV的转基因小鼠的构建 结构蛋白（核心，E1和E2），并显示表达 HCV结构蛋白在该动物中不直接致细胞病变 模型利用DNA免疫，我们能够诱导抗体， 和T细胞对HCV结构蛋白的增殖反应 这些转基因动物。研究正在进行中，以确定 是否可以引发细胞毒性T细胞应答或肝炎 使用这种方法。我们的实验室也在生产转基因 小鼠表达HCV多蛋白全长，并正在开发一种 使用本发明的HCV转基因诱导表达系统 四环素诱导系统。使用LacZ或SV40标签 作为报告基因，我们的初步研究表明， 在转基因小鼠中， 肝脏这些动物将提供有用动物模型， 解决免疫发病机制和细胞病变潜力的问题， 同时也研究HCV基因产物在体内的复制。