在人嵌合肝的免疫缺陷 NOD-Rag1-/-IL2RγC-null (NRG) 延胡索酰乙酰乙酸水解酶 (FAH) 敲除小鼠中模拟 HBV 感染和治疗。
Modeling HBV Infection and Therapy in Immunodeficient NOD-Rag1-/-IL2RgammaC-null (NRG) Fumarylacetoacetate Hydrolase (FAH) Knockout Mice with Human Chimeric Liver.
机构信息
Division of Virology, Pathogenesis and Cancer, Institute of Human Virology, Departments of Pharmacology, Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China.
出版信息
Methods Mol Biol. 2024;2837:199-206. doi: 10.1007/978-1-0716-4027-2_17.
Chimeric mouse models with a humanized liver (Hu-HEP mice) provide a unique tool to study human hepatotropic virus diseases, including viral infection, viral pathogenesis, and anti-viral therapy. Here, we describe a detailed protocol for studying hepatitis B infection in NRG-derived fumarylacetoacetate hydrolase (FAH) knockout mice repopulated with human hepatocytes (FRG-Hu HEP mice). The procedures include (1) maintenance and genotyping of the FRG mice, (2) intrasplenic injection of primary human hepatocytes (PHH), (3) 2-(2-nitro-4-fluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC) drug reduction cycling to improve human hepatocyte repopulation, (4) human albumin detection, and (5) HBV infection and detection. The method is simple and allows for highly reproducible generation of FRG-Hu HEP mice for HBV infection and therapy investigations.
嵌合小鼠模型具有人源化肝脏（Hu-HEP 小鼠），为研究嗜肝人类病毒疾病提供了独特的工具，包括病毒感染、病毒发病机制和抗病毒治疗。在这里，我们描述了一种详细的方案，用于研究 NRG 衍生的延胡索酰乙酰乙酸水解酶（FAH）敲除小鼠中重组人肝细胞（FRG-HuHEP 小鼠）的乙型肝炎感染。该程序包括（1）FRG 小鼠的维持和基因分型，（2）脾内注射原代人肝细胞（PHH），（3）2-（2-硝基-4-氟甲基苯甲酰基）-1,3-环己二酮（NTBC）药物还原循环以改善人肝细胞再殖，（4）人白蛋白检测，（5）HBV 感染和检测。该方法简单，可重复性好，可用于 FRG-HuHEP 小鼠的高效制备，用于 HBV 感染和治疗研究。
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