Current humanized mouse models for studying human immunology and HIV-1 immuno-pathogenesis

查看全文 作　　者：MEISSNER [1]Eric

机构地区：[1]Lineberger Comprehensive Cancer Center,Department of Microbiology and Immunology,School of Medicine,University of North Carolina at Chapel Hill

出　　处：《Science China(Life Sciences)》索引2010年第53卷第2期,共9页

基　　金：supported by the National Natural Science Foundation of China (Grant No. 30872365);the Ministry of Science and Technology Grants (Grant Nos. 2006CB910901 and KSCX2-YW-R-150);the Ministry of Health (Grant Nos. 2009ZX10604 and 2008ZX10002-011);the National Institute of Health (Grant Nos. AI080432, AI041356, AA018009 and AI077454) 摘　　要：A robust animal model for 'hypothesis-testing/mechanistic' research in human immunology and immuno-pathology should meet the following criteria.First,it has well-studied hemato-lymphoid organs and target cells similar to those of humans.Second,the human pathogens establish infection and lead to relevant diseases.Third,it is genetically inbred and can be manipulated via genetic,immunological and pharmacological means.Many human-tropic pathogens such as HIV-1 fail to infect murine cells due to the blocks at multiple steps of their life cycle.The mouse with a reconstituted human immune system and other human target organs is a good candidate.A number of human-mouse chimeric models with human immune cells have been developed in the past 20 years,but most with only limited success due to the selective engraftment of xeno-reactive human T cells in hu-PBL-SCID mice or the lack of significant human immune responses in the SCID-hu Thy/Liv mouse.This review summarizes the current understanding of HIV-1 immuno-pathogenesis in human patients and in SIV-infected primate models.It also reviews the recent progress in the development of humanized mouse models with a functional human immune system,especially the recent progress in the immunodeficient mice that carry a defective gammaC gene.NOD/SCID/gammaC-/(NOG or NSG) or the Rag2-/-/gammaC-/double knockout (DKO) mice,which lack NK as well as T and B cells (NTB-null mice),have been used to reconstitute a functional human immune system in central and peripheral lymphoid organs with human CD34+ HSC.These NTB-hu HSC humanized models have been used to investigate HIV-1 infection,immuno-pathogenesis and therapeutic interventions.Such models,with further improvements,will contribute to study human immunology,human-tropic pathogens as well as human stem cell biology in the tissue development and function in vivo. 关键词：HUMANIZED mouse models HIV-1 NOD/SCID/gammaC-/- Rag2-/-/gammaC-/-

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Current humanized mouse models for studying human immunology and HIV-1 immuno-pathogenesis

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