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Impact of the Mouse IL-2Rγ Chain on Lymphoid Tissue Development and Human Reconstitution in Immunodeficient Mice

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Book cover Humanized Mice for HIV Research

Abstract

Immunodeficient mouse strains with and without a functional mouse interleukin (IL)-2 receptor gamma chain (mouse IL-2Rγ chain) are used to generate humanized mice. Common strains for this purpose include nonobese diabetic (NOD)/severe combined immune deficiency (SCID) mice which have functional mouse IL-2Rγ chain as well as NOD/SCID IL-2Rγc knockout (NOG or NSG) mice and Rag2null IL-2Rγcnull (Rag2γc) mice which lack this molecule. Until recently, the role of the mouse IL-2Rγ chain in lymphoid tissue development and human reconstitution had been underappreciated in the field of humanized mouse research. The goals of this article are to consolidate information on this topic to aid researchers in choosing the most appropriate mouse strain for their specific application from the many strains of immunodeficient mice available. An example of the impact of a functional mouse IL-2Rγ chain on lymphoid tissue development and human reconstitution is the differential intestinal humanization between bone marrow-liver-thymus (BLT) mice generated using NOD/SCID or NSG mice. NOD/SCID-BLT mice, which have an intact mouse IL-2Rγ chain, exhibit significantly higher levels of intestinal humanization versus NSG-BLT mice. This distinction highlights how immunodeficient mouse strains that show improved systemic human engraftment due to the lack of a mouse IL-2Rγ chain may exhibit deficiencies in human engraftment in specific tissues.

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Acknowledgments

This work was supported in part by the University of North Carolina (UNC) Center for AIDS Research grant P30 AI50410; by National Institute of Health grants AI096113 and AI08263 (J.V.G.); and by a Research Fellowship of the Japan Society for the Promotion of Science (T.N.).

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Authors and Affiliations

  1. Division of Infectious Diseases, Department of Medicine, UNC Center for AIDS Research, University of North Carolina School of Medicine, Genetic Medicine Building 2046, 27599-7042, Chapel Hill, NC, USA

    Paul W. Denton, Tomonori Nochi & J. Victor Garcia

  2. Laboratory of Functional Morphology, Tohoku University Graduate School of Agricultural Science, Sendai, Miyagi, Japan

    Tomonori Nochi

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  1. Paul W. Denton
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  2. Tomonori Nochi
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  3. J. Victor Garcia
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Correspondence to Paul W. Denton .

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Editors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska, USA

    Larisa Y. Poluektova

  2. Center for AIDS Research, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

    J. Victor Garcia

  3. Research Center for AIDS Laboratory of Viral Pathogenesis, Kyoto University Institute for Virus Research, Sakyo-ku, Japan

    Yoshio Koyanagi

  4. Division of Hematology, University Hospital Zürich, Zürich, Switzerland

    Markus G. Manz

  5. Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA

    Andrew M. Tager

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Denton, P., Nochi, T., Garcia, J. (2014). Impact of the Mouse IL-2Rγ Chain on Lymphoid Tissue Development and Human Reconstitution in Immunodeficient Mice. In: Poluektova, L., Garcia, J., Koyanagi, Y., Manz, M., Tager, A. (eds) Humanized Mice for HIV Research. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1655-9_6

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