Overcoming Current Limitations in Humanized Mouse Research

被引:115
作者
Brehm, Michael A. [1 ]
Shultz, Leonard D. [2 ]
Luban, Jeremy [1 ]
Greiner, Dale L. [1 ]
机构
[1] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA
[2] Jackson Lab, Bar Harbor, ME 04609 USA
基金
美国国家卫生研究院;
关键词
humanized; immunobiology; infectious disease; IMMUNE-RESPONSES; VAGINAL TRANSMISSION; HIV TRANSMISSION; T-CELLS; MICE; BLOOD; ENGRAFTMENT; INFECTION; SYSTEM; MODEL;
D O I
10.1093/infdis/jit319
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immunodeficient mice engrafted with human cells and tissues have provided an exciting alternative to in vitro studies with human tissues and nonhuman primates for the study of human immunobiology. A major breakthrough in the early 2000s was the introduction of a targeted mutation in the interleukin 2 (IL-2) receptor common gamma chain (IL2rg(null)) into mice that were already deficient in T and B cells. Among other immune defects, natural killer (NK) cells are disrupted in these mice, permitting efficient engraftment with human hematopoietic cells that generate a functional human immune system. These humanized mouse models are becoming increasingly important for preclinical studies of human immunity, hematopoiesis, tissue regeneration, cancer, and infectious diseases. In particular, humanized mice have enabled studies of the pathogenesis of human-specific pathogens, including human immunodeficiency virus type 1, Epstein Barr virus, and Salmonella typhi. However, there are a number of limitations in the currently available humanized mouse models. Investigators are continuing to identify molecular mechanisms underlying the remaining defects in the engrafted human immune system and are generating "next generation" models to overcome these final deficiencies. This article provides an overview of some of the emerging models of humanized mice, their use in the study of infectious diseases, and some of the remaining limitations that are currently being addressed.
引用
收藏
页码:S125 / S130
页数:6
相关论文
共 50 条
[1]   Disseminated and sustained HIV infection in CD34+ cord blood cell-transplanted Rag2-/-γc-/- mice [J].
Baenziger, Stefan ;
Tussiwand, Roxane ;
Schlaepfer, Erika ;
Mazzucchelli, Luca ;
Heikenwalder, Mathias ;
Kurrer, Michael O. ;
Behnke, Silvia ;
Frey, Joachim ;
Oxenius, Annette ;
Joller, Helen ;
Aguzzi, Adriano ;
Manz, Markus G. ;
Speck, Roberto F. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (43) :15951-15956
[2]   A SEVERE COMBINED IMMUNODEFICIENCY MUTATION IN THE MOUSE [J].
BOSMA, GC ;
CUSTER, RP ;
BOSMA, MJ .
NATURE, 1983, 301 (5900) :527-530
[3]   The IL-7 Signaling Pathway Regulates Lymph Node Development Independent of Peripheral Lymphocytes [J].
Chappaz, Stephane ;
Finke, Daniela .
JOURNAL OF IMMUNOLOGY, 2010, 184 (07) :3562-3569
[4]   Inefficient Vaginal Transmission of Tenofovir-Resistant HIV-1 [J].
Chateau, Morgan ;
Swanson, Michael D. ;
Garcia, J. Victor .
JOURNAL OF VIROLOGY, 2013, 87 (02) :1274-1277
[5]   Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice [J].
Chateau, Morgan L. ;
Denton, Paul W. ;
Swanson, Michael D. ;
McGowan, Ian ;
Garcia, J. Victor .
PLOS ONE, 2013, 8 (03)
[6]   GM-CSF and IL-4 Stimulate Antibody Responses in Humanized Mice by Promoting T, B, and Dendritic Cell Maturation [J].
Chen, Qingfeng ;
He, Fang ;
Kwang, Jimmy ;
Chan, Jerry K. Y. ;
Chen, Jianzhu .
JOURNAL OF IMMUNOLOGY, 2012, 189 (11) :5223-5229
[7]  
Christianson SW, 1996, CELL IMMUNOL, V171, P186, DOI 10.1006/cimm.1996.0193
[8]   Expression of HLA Class II Molecules in Humanized NOD.Rag1KO.IL2RgcKO Mice Is Critical for Development and Function of Human T and B Cells [J].
Danner, Rebecca ;
Chaudhari, Snehal N. ;
Rosenberger, John ;
Surls, Jacqueline ;
Richie, Thomas L. ;
Brumeanu, Teodor-Doru ;
Casares, Sofia .
PLOS ONE, 2011, 6 (05)
[9]   IL-2 receptor γ-chain molecule is critical for intestinal T-cell reconstitution in humanized mice [J].
Denton, P. W. ;
Nochi, T. ;
Lim, A. ;
Krisko, J. F. ;
Martinez-Torres, F. ;
Choudhary, S. K. ;
Wahl, A. ;
Olesen, R. ;
Zou, W. ;
Di Santo, J. P. ;
Margolis, D. M. ;
Garcia, J. V. .
MUCOSAL IMMUNOLOGY, 2012, 5 (05) :555-566
[10]   One Percent Tenofovir Applied Topically to Humanized BLT Mice and Used According to the CAPRISA 004 Experimental Design Demonstrates Partial Protection from Vaginal HIV Infection, Validating the BLT Model for Evaluation of New Microbicide Candidates [J].
Denton, Paul W. ;
Othieno, Florence ;
Martinez-Torres, Francisco ;
Zou, Wei ;
Krisko, John F. ;
Fleming, Elisa ;
Zein, Sima ;
Powell, Daniel A. ;
Wahl, Angela ;
Kwak, Youn Tae ;
Welch, Brett D. ;
Kay, Michael S. ;
Payne, Deborah A. ;
Gallay, Philippe ;
Appella, Ettore ;
Estes, Jacob D. ;
Lu, Min ;
Garcia, J. Victor .
JOURNAL OF VIROLOGY, 2011, 85 (15) :7582-7593