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具有嵌合人肝脏的小鼠及其应用。

Mice with Chimeric Human Livers and Their Applications.

作者信息

Douglas Donna N, Kneteman Norman M

机构信息

Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.

出版信息

Methods Mol Biol. 2019;1911:459-479. doi: 10.1007/978-1-4939-8976-8_32.

Abstract

The complete life cycle of the hepatitis C virus (HCV) can be recapitulated in vivo using immunodeficient mice that have had their livers extensively repopulated with human hepatocytes. These human liver chimeric mouse models have enabled the study of many aspects of the HCV life cycle, including antiviral interventions that have helped to shape the curative landscape that is available today. The first human liver chimeric mouse model capable of supporting the HCV life cycle was generated in SCID-uPA mice. Although other human liver chimeric mouse models have since been developed, the SCID-uPA mouse model remains one of the most robust in vivo systems available for HCV studies. This chapter reviews development, validation and application of the SCID-uPA mouse model, and discusses their potential application for studying other liver-centric diseases and pathogens and for the design and testing of vaccine candidates for the eradication of HCV.

摘要

使用肝脏被人类肝细胞大量重新填充的免疫缺陷小鼠,丙型肝炎病毒(HCV)的完整生命周期可以在体内重现。这些人肝嵌合小鼠模型使得对HCV生命周期的许多方面进行研究成为可能,包括抗病毒干预措施,这些干预措施有助于塑造当今可用的治愈格局。第一个能够支持HCV生命周期的人肝嵌合小鼠模型是在SCID-uPA小鼠中构建的。尽管此后又开发了其他一些人肝嵌合小鼠模型,但SCID-uPA小鼠模型仍然是用于HCV研究的最强大的体内系统之一。本章回顾了SCID-uPA小鼠模型的开发、验证和应用,并讨论了它们在研究其他以肝脏为中心的疾病和病原体以及设计和测试用于根除HCV的候选疫苗方面的潜在应用。

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