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2002 Fiscal Year Final Research Report Summary

The studies on the practical application of NOD-sc/d, yc null mice allowing an efficient transplantation of human cells, to human disease models

Research Project

Project/Area Number 13558100
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Laboratory animal science
Research InstitutionCentral Institute for Experimental Animals

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) NAKAHATA Tatsutoshi  Department of Pediatrics, School of Medicine, Kyoto University, Professor, 大学院・医学研究科・小児発達学, 教授 (20110744)
OHNISHI Yasuyuki  Central Institute for Experimental Animals, Laboratory of Oncology, Head, 腫瘍研究室, 室長 (70201382)
HIOKI Kyoji  Central Institute for Experimental Animals, Laboratory of Immunology, Head, 飼育技術研究室, 室長 (80208735)
TANAKA Yuetsu  Department of Infectious Disease and Immunology, Okinawa-Asia Research Center of Medical Science, University of the Ryukyu, Professor, 医・付属沖縄アジア医学研究センター・感染免疫部門, 教授 (30163588)
KOYANAGI Yoshio  Department of Virology, School of Medicine, Tohoku University, Professor, 大学院・医学研究科・微生物, 教授 (80215417)
Project Period (FY) 2001 – 2002
Keywordsexperimental animals / NOD-scid. γc null mice / Immunodeficiency / Xenotransplantation / CD34+ stem cells / HIV-1 / HTLV-1
Research Abstract

1. We have eliminated C57BL/6 genes which originated frolL-2Rγ KO mice and still remained in NOG mice, by further backcross mating to NOD/Shi- scid mice. The reproduction efficacy of NOG mice was almost same to that of NOD/Shi- scid mice. The reproduction efficacy of NOG mice was almost same to that of NOD/Shi- scid mice.
2. After intravenous inoculation of human cord blood CD34^+ cells, the NOG mice allowed the extremely higher growth rate of human cells when compared with NOD/Shi-scid mice. In addition, human CD4^+ T and CD8^+ T cells could differentiate in these mice. Human B cells also generated and reproduced human immunoglobulins in NOG mice.
3. When HIV-1 was inoculated to PBL-NOG-hu mice, which were inoculated with human PBMC, the significantly high level of HIV-1 p24 gag as well as HIV-1 RNA in plasma and cell-associated HIV-1 DNA were detected, respectively. Simultaneously, the remarkable level of human CD4+ cell depletion was observed.
4. In HTLV-1 infection NOG model, two to 3 … More weeks after subcutaneous inoculation of HTLV-1 infected cell lines in the post-auricular region of NOG mice, a visible tumor developed in the site. Almost all cell lines formed a progressively growing large tumor mass with leukemic infiltration of cells in various organs.
5. Seven weeks after intravenous inoculation of U266 cells, which were IL-6 dependent human myeloma cell line, to NOG mice, U226 cells massively infiltrated in bone marrow of NOG mice and also invaded into the spiral cord plexus, and finally caused hind leg paralysis, weight loss and distress as observed in human patients.
6. NOG mice showed high growth rate of primary human tumor transplantation. When human pancreas tumor cells, i.e. Capan-1 and PANC-1, were inoculated into the mouse spleen, the high metastasis rates in liver were observed in NOG mice but not NOD/Shi- scid mice. These results indicated that NOG mice were extremely useful tools for human disease model.
These results indicated that NOG mice were extremely useful tools for human disease model. Less

  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Ito, M.: "NOD/SCID/gamma(c)(null) mouse : an excellent recipient mouse model for engraftment of human cells"Blood.. 100. 3175-3182 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saito, Y.: "The in vivo development of human T cells from CD34(+) cells in the murine thymic environment"Int Immunol.. 14. 1113-1124 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ma, F.: "Growth of human T cell acute lymphoblastic leukemia lymphoblasts in NOD/SCID mouse fetal thymus organ culture"Leukemia. 16. 1541-1548 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wada M: "Tunica interna endothelial cell kinase expression and hematopoietic and angiogenic potentials in cord blood CD34+ cells"Int J Hematol. 77. 245-252 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miura, Y: "Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection"Proc.Natl.Acad.Sci. USA.. 100. 2777-22782 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ebihara, Y: "Reconstitution of human haematopoiesis in non-obese diabetic/severe combined immunodeficient mice by clonal cells expanded from single CD34+CD38-cells expressing FlK2/Flt3"Br.J.Haematol.. 119. 525-534 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Dewan, Z.: "Rapid Tumor Formation of HTLV-I-infected Cell Lines in Novel NOD-SCID/gc^<null> (NOG) Mice : Suppression by an Inhibitor Against NF-kB"J.Virol.. 77. 5286-5294 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hiramatsu H.: "Complete reconstitution of human lymphocytes from cord blood CD34^+ cells using the NOD/SCID/g_c^<null> mice model"Blood. 101. 10 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miura Y: "Critical Contribution of Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) to Apoptosis of Human CD4(+) T Cells in HIV-1-infected hu-PBL-NOD-SCID Mice"J Exp Med.. 193. 651-660 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ueda T: "Hematopoietic Capability of CD34+ Cord Blood Cells : A Comparison With CD34+ Adult Bone Marrow Cells"Int J Hematol.. 73. 457-462 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Dewan MZ, Terashima K, Taruishi M, Hasegawa H, Ito M, Tanaka Y, Mori N, Sata T, Koyanagi Y, Maeda M, Kubuki Y, Okayama A, Fujii M, Yamamoto N. Rapid: "Tumor Formation of Human T-Cell Leukemia Virus Type 1-Infected Cell Lines in Novel NOD-SCID/gammac(null) Mice: Suppression by an Inhibitor against NF-kappaB."J Virol.. 77. 5286-5294 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hiramatsu H, Nishikomori R, Heike T, Ito M, Kobayashi K, Katamura K, Nakahata T.: "Complete reconstitution of human lymphocytes from cord blood CD34+ cells using the NOD/SCID/{gamma}cnuil mice model."Blood.. 10. 10 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miura Y, Misawa N, Kawano Y, Okada H, Inagaki Y, Yamamoto N, Ito M, Yagita H, Okumura K, Mizusawa H, Koyanagi Y.: "Tumor necrosis factor-related apoptosis-inducing ligand induces neuronal death in a murine model of HIV central nervous system infection."Proc Natl Acad Sci U S A.. 100. 2777-2782 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato Y, Terada Y, Utsunomiya H, Koyanagi Y, Ito M, Miyoshi I, Suzuki T, Sasano H, Murakami T, Yaegashi N, Okamura K.: "Immunohistochemical localization of steroidogenic enzymes in human follicle following xenotransplantation of the human ovarian cortex into NOD-SCID mice"Mol Reprod Dev.. 65. 67-72 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Wada M, Ebihara Y, Ma F, Yagasaki H, Ito M, Takahashi T, Mugishima H, Takahashi S, Tsuji K.: "Tunica interna endothelial cell kinase expression and hematopoietic and angiogenic potentials in cord blood CD34+ cells."Int J Hematol.. 77. 245-252 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] EbiharaY, Wada M, UedaT,Xu MJ, ManabeA,Tanaka R, Ito M, Mugishima H, Asano S, Nakahata T, Tsuji K.: "Reconstitution of human haematopoiesis in non-obese diabetic/severe combined immunodeficient mice by clonal cells expanded from single CD34+CD38- cells expressing Flk2/Flt3"BrJ Haematol.. 119. 525-534 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ito M, Hiramatsu H, Kobayashi K, Suzue K, Kawahata M, Hioki K, UeyamaY, Koyanagi Y, Sugamura K, Tsuji K, Heike T, Nakahata T.: "NOD/SCID/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells."Blood. 100. 3175-3182 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ma F, Manabe A, Wang D, Ito M, Kikuchi A, Wada M, Ohara A, Hosoya R, Asano S, Tsuji K.: "Growth of human T cell acute lymphoblastic leukemia lymphoblasts in NOD/SCID mouse fetal thymus organ culture."Leukemia. 6. 1541-1548 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saito Y, Kametani Y, Hozumi K, Mochida N, Ando K, Ito M, Nomura T, Tokuda Y, Makuuchi H, Tajima T, Habu S.: "The in vivo development of human T cells from CD34(+) cells in the murine thymic environment."Int Immunol. 14. 1113-1124 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kosugi H, Ito M, Yamamoto Y, Towatari M, Ueda R, Saito H, Naoe T.: "In vivo Effects of a Histone Deacetylase Inhibitor, FK228, on Human Acute Promyelocytic Leukemia in NOD / Shi-scid / scid Mice."Jpn J Cancer Res.. 92. 529-536 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ma F, Wada M, Yoshino H, Ebihara Y, Ishii T, Manabe A, Tanaka R, Maekawa T, Ito M, Mugishima H, Asano S, Nakahata T, Tsuji K.: "Development of human lymphohematopotetic stem and progenitor cells defined by expression of CD34 and CD81."Blood. 97. 3755-3762 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miura Y, Misawa N, Maeda N, Inagaki Y, Tanaka Y, Ito M, Kayagaki N, Yamamoto N, Yagita H, Mizusawa H, Koyanagi Y.: "Critical Contribution of Tumor Necrosis Factor-related Apoptosis- inducing Ligand (TRAIL) to Apoptosis of Human CD4(+) T Cells in HIV-1- infected hu-PBL- NOD-SCID Mice."J Exp Med.. 193. 651-660 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] UedaT, Yoshida M, Yoshino H, Kobayashi K, M. K, EbiharaY, Ito M,Asano S, Nakahata T, Tsuji K.: "Hematopoietic Capability of CD34+ Cord Blood Cells: A Comparison With CD34+ Adult Bone Marrow Cells."Int J Hematoi.. 73. 457-462 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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