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The utilization of humanized mouse models for the study of human retroviral infections

Rachel Van Duyne,#1 Caitlin Pedati,#2 Irene Guendel,2 Lawrence Carpio,2 Kylene Kehn-Hall,2 Mohammed Saifuddin,3 and Fatah Kashanchicorresponding author2


1Microbiology, Immunology, and Tropical Medicine Program, The George Washington University School of Medicine, Washington, DC 20037, USA
2Department of Microbiology, Immunology, and Tropical Medicine, The George Washington University School of Medicine, Washington, DC 20037, USA
3CONRAD, Eastern Virginia Medical School, 1911 Fort Myer Drive, Suite 900, Arlington, VA 22209, USA
corresponding authorCorresponding author.
#Contributed equally.
Rachel Van Duyne: [e-mail]; Caitlin Pedati: [e-mail]; Irene Guendel: [e-mail]; Lawrence Carpio: [e-mail]; Kylene Kehn-Hall: [e-mail]; Mohammed Saifuddin: [e-mail]; Fatah Kashanchi: [e-mail]

Received March 24, 2009; Accepted August 12, 2009.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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* Other Sections?
o Abstract
o HIV-1 Pathogenesis
o Comparison of animal models for the study of retroviral infection
o A brief history of humanized mouse models
o Graft vs. Host disease in humanized mouse models
o Humanized murine models of HIV-1 infection
o NOD-SCID models
o NOD/SCID IL2r?-/- mouse model and HIV-1 infection
o Humanized Rag2-/-?c-/- Mice and HIV-1 infection
o Humanized murine models for HTLV-1 infection
o Humanized mice and co-infection models
o Conclusion
o Competing interests
o Authors' contributions
o References

Abstract
The development of novel techniques and systems to study human infectious diseases in both an in vitro and in vivo settings is always in high demand. Ideally, small animal models are the most efficient method of studying human afflictions. This is especially evident in the study of the human retroviruses, HIV-1 and HTLV-1, in that current simian animal models, though robust, are often expensive and difficult to maintain. Over the past two decades, the construction of humanized animal models through the transplantation and engraftment of human tissues or progenitor cells into immunocompromised mouse strains has allowed for the development of a reconstituted human tissue scaffold in a small animal system. The utilization of small animal models for retroviral studies required expansion of the early CB-17 scid/scid mouse resulting in animals demonstrating improved engraftment efficiency and infectivity. The implantation of uneducated human immune cells and associated tissue provided the basis for the SCID-hu Thy/Liv and hu-PBL-SCID models. Engraftment efficiency of these tissues was further improved through the integration of the non-obese diabetic (NOD) mutation leading to the creation of NODSCID, NOD/Shi-scid IL2r?-/-, and NOD/SCID ß2-microglobulinnull animals. Further efforts at minimizing the response of the innate murine immune system produced the Rag2-/-?c-/- model which marked an important advancement in the use of human CD34+ hematopoietic stem cells. Together, these animal models have revolutionized the investigation of retroviral infections in vivo.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743631/