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2009 Fiscal Year Final Research Report

Development of novel humanized NOG mice producing human IgG antibody

Research Project

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Project/Area Number 19700373
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Laboratory animal science
Research InstitutionCentral Institute for Experimental Animals

Principal Investigator

ITO Ryoji  Central Institute for Experimental Animals, 免疫研究室, 研究員 (60425436)

Project Period (FY) 2007 – 2009
Keywordsヒト化マウス / ヒト型抗体
Research Abstract

The purpose in this research is to produce human IgG antibody using humanized NOG mice that were reconstituted with the human immune system. In this study, we attempted to develop five strains of transgenic (Tg) NOG mice carrying human genes (hIL-7, hLymphotoxin, hCXCL13, hIL-6 and hIFNγ), which are important for the development and functional maturation of immune cells. We confirmed the expression of transgenes, hIL-7, hLymphotoxin and hIL-6 in three strains of Tg mice. Hematopoietic stem cell transplantation into hLymphotoxin Tg mice and substitution of the genetic background of hIL-6 Tg mice in NOG mice are currently underway. We report here that the results obtained by hIL-7 Tg NOG mice reconstituted with the human immune system. We analyzed engraftment and differentiation of human T and B cells in hIL-7 Tg mice by flow cytometry. As a result, the engraftment rate of human cells and differentiation into T and B cells did not differ between hIL-7 Tg NOG and control non-Tg NOG mice. To determine the potential of cell growth of human T cells developed in hIL-7 Tg NOG mice, we isolated human T cells from the spleen and stimulated them with anti-human CD3 and CD28 antibodies in vitro. As a result, human T cells from hIL-7 Tg NOG mice showed significantly higher proliferation than those from non-Tg NOG mice. This result suggests that IL-7 signaling can induce the growth phase, in differentiated human T cells, which presumably become capable of rapid elimination of foreign pathogens. Therefore, hIL-7 Tg NOG mice have potential as a useful tool in the form of humanized mice reconstituted with the human immune system. We are attempting to produce human IgG antibodies by immunization of T cell dependent antigens using hIL-7 Tg NOG mice.

  • Research Products

    (8 results)

All 2009 2008

All Journal Article (3 results) Presentation (5 results)

  • [Journal Article] The analysis of the functions of human B and T cells in humanized NOD/shi-scid/ gammac (null) (NOG) mice (hu-HSC NOG mice)2009

    • Author(s)
      Watanabe Y, Takahashi T, Okajima A, Shiokawa M, Ishii N, Katano I, Ito R, Ito M, Minegishi M, Minegishi N, Tsuchiya S, Sugamura K.
    • Journal Title

      Int Immunol 21

      Pages: 843-58

  • [Journal Article] Highly sensitive model for xenogenic GVHD using severe immunodeficient NOG mice2009

    • Author(s)
      Ito R, Katano I, Kawai K, Hirata H, Ogura T, Kamisako T, Eto T, Ito M.
    • Journal Title

      Transplantation 15

      Pages: 1654-8

  • [Journal Article] Antigen-specific antibody production of human B cells in NOG mice reconstituted with the human immune system2008

    • Author(s)
      Ito R, Shiina M, Saito Y, Tokuda Y, Kametani Y, Habu S.
    • Journal Title

      Curr Top Microbiol Immunol 324(Review)

      Pages: 95-107

  • [Presentation] IFNγ producing killer dendritic cells have a suppressive effect on xeno-GVHD in NOG mice2009

    • Author(s)
      Ryoji Ito, Ikumi Katano, Kenji Kawai, Mamoru Ito
    • Organizer
      第39回日本免疫学会
    • Year and Date
      20091200
  • [Presentation] High sensitivity to xeno-GVHD in severely immunodeficient NOG mice is attributable to dysfunction of dendritic cells2009

    • Author(s)
      Ryoji Ito, Ikumi Katano, Tomoyuki Ogura, Kenji Kawai, Mamoru Ito
    • Organizer
      2nd International Workshop on Humanized Mice
    • Year and Date
      20090400
  • [Presentation] Dendritic cells have a suppressive effect on xeno-GVHD in novel immunodeficient NOG mice2008

    • Author(s)
      Ryoji ITO, Ikumi KATANO, Tomoyuki OGURA, Kenji KAWAI, Mamoru ITO
    • Organizer
      10th International Symposium on Dendritic Cells
    • Year and Date
      20081000
  • [Presentation] ヒトDelta-like 1トランスジェニックNOGマウスに発症する骨硬化はヒト造血系の再構築を抑制する2008

    • Author(s)
      伊藤亮治、小倉智幸、入江奈緒子、松尾光一、垣生園子、伊藤守
    • Organizer
      第26回日本骨代謝学会
    • Year and Date
      20081000
  • [Presentation] 重度免疫不全NOGマウスを用いた高GVHD感受性モデル2008

    • Author(s)
      伊藤亮治、小倉智幸、川井健司、伊藤守
    • Organizer
      第55回日本実験動物学会
    • Year and Date
      20080500

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Published: 2011-06-18   Modified: 2016-04-21  

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