在移植了人肝细胞的免疫缺陷型NOD-Rag1-/-IL2RγC基因敲除（NRG）富马酰乙酰乙酸水解酶（Fah）基因敲除小鼠中研究乙肝病毒感染与治疗
Studying HBV Infection and Therapy in Immune-Deficient NOD-Rag1-/-IL2RgammaC-null (NRG) Fumarylacetoacetate Hydrolase (Fah) Knockout Mice Transplanted with Human Hepatocytes.
作者信息
Li Feng, Nio Kouki, Yasui Fumihiko, Murphy Christopher M, Su Lishan
机构信息
Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
出版信息
Methods Mol Biol. 2017;1540:267-276. doi: 10.1007/978-1-4939-6700-1_23.
Chimeric mouse models with a humanized liver provide a unique tool to study hepatic virus diseases, including viral infection, viral pathogenesis, and antiviral therapy. Here we describe a detailed protocol for studying hepatitis B infection in NRG-derived fumarylacetoacetate hydrolase (Fah) knockout mice repopulated with human hepatocytes. The procedures include (1) maintenance and genotyping of the homozygous NRG-fah/fah mutant mice (NRG/F), (2) intrasplenic injection of human hepatocytes, (3) 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 NRG/F-hu Hep mice for studying HBV infection and therapy.
具有人源化肝脏的嵌合小鼠模型为研究肝脏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。在此，我们描述了一种详细的方案，用于研究用人类肝细胞重新填充的NRG衍生的富马酰乙酰乙酸水解酶（Fah）基因敲除小鼠中的乙型肝炎感染。这些步骤包括：（1）纯合NRG-fah/fah突变小鼠（NRG/F）的饲养和基因分型；（2）人肝细胞的脾内注射；（3）NTBC药物减量循环以改善人肝细胞的重新填充；（4）人白蛋白检测；以及（5）HBV感染和检测。该方法简单，能够高度可重复地产生用于研究HBV感染和治疗的NRG/F-hu Hep小鼠。
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