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2010 Fiscal Year Final Research Report

Basic study to establish "humanized animal model" by improvement and modification of severely immunodeficient NOG mouse

Research Project

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Project/Area Number 18100005
Research Category

Grant-in-Aid for Scientific Research (S)

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

Principal Investigator

ITO Mamoru  Central Institute for Experimental Animals, 免疫研究室, 室長 (00176364)

Co-Investigator(Kenkyū-buntansha) HABU Sonoko  東海大学, 医学部, 教授 (30051618)
ANDO Kiyoshi  東海大学, 医学部, 教授 (70176014)
MIYAKAWA Yoshitaka  慶応義塾大学, 医学部, 講師 (50250238)
SUZUE Kazutomo  群馬大学, 医学研究科, 講師 (00333485)
SUEMIZU Hiroshi  (財)実験動物中央研究所, 分子解析研究室, 室長 (40332209)
Project Period (FY) 2006 – 2009
Keywords病態モデル / 免疫不全マウス / ヒト化動物モデル
Research Abstract

Severe immunodeficient NOG mice reported by us in 2002 show extremely high engraftment potential for xenogenic cells and tissues. Therefore, these mice enable us to generate "humanized mice" in which human cells and tissues act in the same way in humans by transplantation of human cells and tissues into NOG mice. The objective of this project is to improve immunodeficient mice including NOG mice by introducing human genes or by inactivating mouse genes to facilitate the generation of humanized mice. In the 4-year project period, we have newly established 33 strains of immunodeficient mice, and are working on 10 strains are in progress. By using NOG mice and these improved immunodeficient mice, we established various humanized models including those for infectious diseases, GVHD, cancer metastasis, human liver metabolism and stem cell differentiation. These models may be useful to evaluate new drug efficacy and safety, and also to analyze the mechanisms underlying human diseases.

  • Research Products

    (38 results)

All 2009 2008 2007 2006 Other

All Journal Article (20 results) (of which Peer Reviewed: 20 results) Presentation (17 results) Remarks (1 results)

  • [Journal Article] Selective infection of CD4+ effector memory T lymphocytes leads to preferential depletion of memory T lymphocytes in R5 HIV-1-infected humanized NOD/SCID/IL-2Rgammanull mice.2009

    • Author(s)
      Nie C., K.Sato, N.Misawa, H.Kitayama, H.Fujino, H.Hiramatsu, T.Heike, T.Nakahata, Y.Tanaka, M.Ito, Y.Koyanagi
    • Journal Title

      Virology 394

      Pages: 64-72

    • Peer Reviewed
  • [Journal Article] Effects of liposome-encapsulated hemoglobin on human immune system: evaluation in immunodeficient mice reconstituted with human cord blood stem cells.2009

    • Author(s)
      Kawaguchi A.T., Y.Kametani, S.Kato, H.Furuya, K.Tamaoki, S.Habu
    • Journal Title

      Artif Organs 33

      Pages: 169-176

    • Peer Reviewed
  • [Journal Article] Highly sensitive model for xenogenic GVHD using severe immunodeficient NOG mice.2009

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

      Transplantation 87

      Pages: 1654-1658

    • Peer Reviewed
  • [Journal Article] Interferon-alpha 2b-induced thrombocytopenia is caused by inhibition of platelet production but not proliferation and endomitosis in human megakaryocytes.2008

    • Author(s)
      Yamane A., T.Nakamura H.Suzuki M.Ito, Y.Ohnishi, Y.Ikeda, Y.Miyakawa
    • Journal Title

      Blood 112

      Pages: 542-550

    • Peer Reviewed
  • [Journal Article] A new humanized mouse model of Epstein-Barr virus infection that reproduces persistent infection, lymphoproliferative disorder, and cell-mediated and humoral immune responses.2008

    • Author(s)
      Yajima M., K.Imadome, A.Nakagawa, S.Watanabe, K.Terashima, H.Nakamura, M.Ito, N.Shimizu, M.Honda, N.Yamamoto, S.Fujiwara
    • Journal Title

      J Infect Dis 198

      Pages: 673-682

    • Peer Reviewed
  • [Journal Article] Quiescent human hematopoietic stem cells in the bone marrow niches organize the hierarchical structure of hematopoiesis.2008

    • Author(s)
      Yahata T., Y.Muguruma, S.Yumino, Y.Sheng, T.Uno, H.Matsuzawa, M.Ito, S.Kato, T.Hotta, K.Ando
    • Journal Title

      Stem Cells 26

      Pages: 3228-3236

    • Peer Reviewed
  • [Journal Article] Development of human Graafian follicles following transplantation of human ovarian tissue into NOD/SCID/gammacnull mice.2008

    • Author(s)
      Terada Y., Y.Terunuma-Sato, T.Kakoi-Yoshimoto, H.Hasegawa, T.Ugajin, Y.Koyanagi, M.Ito, T.Murakami, H.Sasano, N.Yaegashi, K.Okamura
    • Journal Title

      Am J Reprod Immunol 60

      Pages: 534-540

    • Peer Reviewed
  • [Journal Article] Establishing EGFP congenic mice in a NOD/Shi-scid IL2Rg(null) (NOG) genetic background using a marker-assisted selection protocol (MASP).2008

    • Author(s)
      Suemizu H., C.Yagihashi, T.Mizushima, T.Ogura, T.Etoh, K.Kawai, M.Ito
    • Journal Title

      Exp Anim 57

      Pages: 471-477

    • Peer Reviewed
  • [Journal Article] Establishment of a humanized model of liver using NOD/Shi-scid IL2Rgnull mice.2008

    • Author(s)
      Suemizu H., M.Hasegawa, K.Kawai, K.Taniguchi, M.Monnai, M.Wakui, M.Suematsu, M.Ito, G.Peltz, M.Nakamura
    • Journal Title

      Biochem Biophys Res Commun 377

      Pages: 248-252

    • Peer Reviewed
  • [Journal Article] Humanized mice for human retrovirus infection.2008

    • Author(s)
      Koyanagi Y., Y.Tanaka, M.Ito, N.Yamamoto
    • Journal Title

      Curr Top Microbiol Immunol 324

      Pages: 133-148

    • Peer Reviewed
  • [Journal Article] Antigen-specific antibody production of human B cells in NOG mice reconstituted with the human immune system.2008

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

      Curr Top Microbiol Immunol 324

      Pages: 95-107

    • Peer Reviewed
  • [Journal Article] NOD/Shi-scid IL2rgamma(null) (NOG) mice more appropriate for humanized mouse models.2008

    • Author(s)
      Ito M., K.Kobayashi, T.Nakahata
    • Journal Title

      Curr Top Microbiol Immunol 324

      Pages: 53-76

    • Peer Reviewed
  • [Journal Article] Humanizing bone marrow in immune-deficient mice.2008

    • Author(s)
      Ando K., Y.Muguruma, T.Yahata
    • Journal Title

      Curr Top Microbiol Immunol 324

      Pages: 77-86

    • Peer Reviewed
  • [Journal Article] Hematopoietic stem cell-engrafted NOD/SCID/IL2Rgamma null mice develop human lymphoid systems and induce long-lasting HIV-1 infection with specific humoral immune responses.2007

    • Author(s)
      Watanabe S., K.Terashima, S.Ohta, S.Horibata, M.Yajima, Y.Shiozawa, M.Z.Dewan, Z.Yu, M.Ito, T.Morio, N.Shimizu, M.Honda, N.Yamamoto
    • Journal Title

      Blood 109

      Pages: 212-218

    • Peer Reviewed
  • [Journal Article] Identification of a key molecular regulator of liver metastasis in human pancreatic carcinoma using a novel quantitative model of metastasis in NOD/SCID/gammacnull (NOG) mice.2007

    • Author(s)
      Suemizu H., M.Monnai, Y.Ohnishi, M.Ito, N.Tamaoki, M.Nakamura
    • Journal Title

      Int J Oncol 31

      Pages: 741-751

    • Peer Reviewed
  • [Journal Article] Human cord blood CD34+ cells develop into hepatocytes in the livers of NOD/SCID/gamma(c)null mice through cell fusion.2007

    • Author(s)
      Fujino H., H.Hiramatsu, A.Tsuchiya, A.Niwa, H.Noma, M.Shiota, K.Umeda, M.Yoshimoto, M.Ito, T.Heike, T.Nakahata
    • Journal Title

      Faseb J 21

      Pages: 3499-3510

    • Peer Reviewed
  • [Journal Article] Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic stem cells.2006

    • Author(s)
      Yahata T., S.Yumino, Y.Seng, H.Miyatake, T.Uno, Y.Muguruma, M.Ito, H.Miyoshi, S.Kato, T.Hotta, K.Ando
    • Journal Title

      Blood 108

      Pages: 2446-2454

    • Peer Reviewed
  • [Journal Article] A novel nonpeptidyl human c-Mpl activator stimulates human megakaryopoiesis and thrombopoiesis.2006

    • Author(s)
      Nakamura T., Y.Miyakawa, A.Miyamura, A.Yamane, H.Suzuki, M.Ito, Y.Ohnishi, N.Ishiwata, Y.Ikeda, N.Tsuruzoe
    • Journal Title

      Blood 107

      Pages: 4300-4307

    • Peer Reviewed
  • [Journal Article] Reconstitution of the functional human hematopoietic microenvironment derived from human mesenchymal stem cells in the murine bone marrow compartment.2006

    • Author(s)
      Muguruma Y., T.Yahata, H.Miyatake, T.Sato, T.Uno, J.Itoh, S.Kato, M.Ito, T.Hotta, K.Ando
    • Journal Title

      Blood 107

      Pages: 1878-1887

    • Peer Reviewed
  • [Journal Article] Development of human-human hybridoma from anti-Her-2 peptide-producing B cells in immunized NOG mouse.2006

    • Author(s)
      Kametani Y., M.Shiina, I.Katano, R.Ito, K.Ando, K.Toyama, H.Tsukamoto, T.Matsumura, Y.Saito, D.Ishikawa, T.Taki, M.Ito, K.Imai, Y.Tokuda, S.Kato, N.Tamaoki, S.Habu
    • Journal Title

      Exp Hematol 34

      Pages: 1239-1247

    • Peer Reviewed
  • [Presentation] 免疫不全マウス4系統でのヒト造血幹細胞移入後の生着および分化能の比較2009

    • Author(s)
      片野いくみ
    • Organizer
      第56回日本実験動物学会総会
    • Place of Presentation
      大宮
    • Year and Date
      20090514-20090516
  • [Presentation] NOGマウスを用いたヒト肝臓モデルの確立2009

    • Author(s)
      末水洋志
    • Organizer
      第56回日本実験動物学会総会
    • Place of Presentation
      大宮
    • Year and Date
      20090514-20090516
  • [Presentation] Mouse models as "humanized mice"2009

    • Author(s)
      Ito M.
    • Organizer
      2^<nd> IWHM
    • Place of Presentation
      Holland
    • Year and Date
      20090403-20090406
  • [Presentation] A novel severe immunodeficient NOG mice with the c-kit, W^v mutation showing high engraftment of human cells without irradiation2009

    • Author(s)
      Katano I
    • Organizer
      2^<nd> IWHM
    • Place of Presentation
      Holland
    • Year and Date
      20090403-20090406
  • [Presentation] Establishing a humanized model of the liver using NOG mice2009

    • Author(s)
      Suemizu H
    • Organizer
      2^<nd> IWHM
    • Place of Presentation
      Holland
    • Year and Date
      20090403-20090406
  • [Presentation] The analysis of the functions of human b and T cells in humanized NOD/Shi-scid/gcnull (NOG) mice (hu-HSC NOG mice).2009

    • Author(s)
      Takahashi T
    • Organizer
      2^<nd> IWHM
    • Place of Presentation
      Holland
    • Year and Date
      20090403-20090406
  • [Presentation] C-kit変異をもつ重度免疫不全NOG-Wvマウスはヒト細胞の高い生着性を示す2008

    • Author(s)
      片野いくみ
    • Organizer
      第38回日本免疫学会
    • Place of Presentation
      京都
    • Year and Date
      20081201-20081203
  • [Presentation] NOGマウスにおける樹状細胞の機能低下は高度Xeno-GVHD発症の要因となる2008

    • Author(s)
      伊藤亮治
    • Organizer
      第38回日本免疫学会
    • Place of Presentation
      京都
    • Year and Date
      20081201-20081203
  • [Presentation] Facilitating the human B cell development in humanized NOG mice.2008

    • Author(s)
      Watanabe Y
    • Organizer
      第38回日本免疫学会
    • Place of Presentation
      京都
    • Year and Date
      20081201-20081203
  • [Presentation] EBV感染モデルマウスの確立と活性化CD8+T細胞の誘導2008

    • Author(s)
      佐藤桂
    • Organizer
      第38回日本免疫学会
    • Place of Presentation
      京都
    • Year and Date
      20081201-20081203
  • [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
    • Organizer
      第26回骨代謝学会
    • Place of Presentation
      大坂
    • Year and Date
      20081029-20081031
  • [Presentation] Dendritic cells have a suppressive effect on xeno-GVHD in novel immunodeficient NOG mice2008

    • Author(s)
      伊藤亮治
    • Organizer
      第10回国際樹状細胞シンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      20081001-20081005
  • [Presentation] Interferon-alpha2b-induced thrombocytopenia is caused by inhibition of platelet production but not proliferation and endomitosis in human megakaryocytes.2008

    • Author(s)
      Yamane A
    • Organizer
      Platelets 2008 International Symposium
    • Place of Presentation
      米国
    • Year and Date
      20081000
  • [Presentation] Establishment of a novel cell line and animal model for a rare case of plasmablastic lymphoma.2008

    • Author(s)
      Matsuki E
    • Organizer
      第32回Annual Meeting of the International Society of Hematology
    • Place of Presentation
      タイ
    • Year and Date
      20081000
  • [Presentation] Characterization of human lymphocytes in humanized NOG mice.2007

    • Author(s)
      Watanabe Y
    • Organizer
      第37回日本免疫学会
    • Place of Presentation
      東京
    • Year and Date
      20071120-20071122
  • [Presentation] Development of the novel thrombopoietin receptor activator NIP-004 to increase human platelets.2007

    • Author(s)
      Miyakawa Y
    • Organizer
      54.Basic study and clinical application of the human stem cell biology and immunology. 21st century center of excellence (COE) program.International symposium 2007
    • Place of Presentation
      東京
    • Year and Date
      20071100
  • [Presentation] Liposome-Encapsulated Hemoglobin (TRM645) Does Not Interfere with The Immune Response to Bacterial Entrotoxins in Mice Reconstitued with Human Immune System.2006

    • Author(s)
      A.Kawaguchi
    • Organizer
      第13回日本血液代替物学会年次大会
    • Place of Presentation
      東京
    • Year and Date
      20060824-20060825
  • [Remarks] ホームページ等

    • URL

      http://www.ciea.or.jp

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Published: 2012-01-26   Modified: 2016-04-21  

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