Generation of a humanized mouse model with both human immune system and liver cells to model hepatitis C virus infection and liver immunopathogenesis.
Generation of a humanized mouse model with both human immune system and liver cells to model hepatitis C virus infection and liver immunopathogenesis.
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DOI：
10.1038/nprot.2012.083
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发表时间：
2012-09
期刊：
影响因子：
14.8
通讯作者：
Su, Lishan
中科院分区：
文献类型：
--
作者：
Bility, Moses T.;Zhang, Liguo;Washburn, Michael L.;Curtis, T. Anthony;Kovalev, Grigoriy I.;Su, Lishan
建立一个能够准确再现嗜肝性病原体（包括丙型肝炎病毒（HCV）感染和免疫发病机制）的小动物模型对于研究肝炎病毒诱导的肝病和开发治疗药物至关重要。该方案描述了我们最近开发的人源化小鼠模型，用于研究HCV和其他嗜肝性感染，人类免疫应答以及肝炎和肝纤维化。第一个5-h阶段是从胎肝分离人肝祖细胞和造血干细胞。接着，将分离的祖细胞/干细胞移植到AFC 8免疫缺陷小鼠。这通常需要2小时。然后用小鼠肝硬化诱导AFC 8二聚化剂处理移植的小鼠1个月，并再放置2个月，以允许人肝和免疫细胞生长以及系统重建和发育，然后接种HCV临床分离株。从接种后约2个月开始观察到HCV感染、人体免疫应答和肝脏疾病的高发率。
Establishing a small animal model that accurately recapitulates hepatotropic pathogens, including hepatitis C virus (HCV) infection and immunopathogenesis, is essential for the study of hepatitis virus–induced liver disease and for therapeutics development. This protocol describes our recently developed humanized mouse model for studying HCV and other hepatotropic infections, human immune response and hepatitis and liver fibrosis. The first 5-h stage is the isolation of human liver progenitor and hematopoietic stem cells from fetal liver. Next, AFC8 immunodeficient mice are transplanted with the isolated progenitor/stem cells. This generally takes 2 h. The transplanted mice are then treated for a month with the mouse liver apoptosis–inducing AFC8 dimerizer and left for an additional 2-month period to permit human liver and immune cell growth as well as system reconstitution and development before inoculation with HCV clinical isolates. HCV infection, human immune response and liver disease are observed with high incidence from approximately 2 months after inoculation.
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