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Lymphocyte deficient mice as hosts for xenograft of human cells

Research Project

Project/Area Number 10559007
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 広領域
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NAKAMURA Masataka  Tokyo Medical and Dental University, Human Gene Sciences Center, Professor, 疾患遺伝子実験センター, 教授 (30180392)

Co-Investigator(Kenkyū-buntansha) ITO Mamoru  Central Institute for Experimental Animals, Laboratory of Immunology, Senior Scientist, 免疫研究室, 主任研究員 (00176364)
TANAKA Yuuetsu  Ryukyus University, Faculty of Medicine, Professor, 医学部, 教授 (30163588)
HIROKAWA Katsuiku  Tokyo Medical and Dental University, Medical Research Division, Professor, 医学系研究科, 教授 (00014093)
小柳 義夫  東京医科歯科大学, 医学部, 助教授 (80215417)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥4,200,000 (Direct Cost: ¥4,200,000)
Keywordsimmunodeficiency / animal model / common γchain / RAG1・RAG2 / knock-out mouse / human cancer / NK細胞
Research Abstract

Naturally and artificially generated mutant mice are useful in human disease studies. We have established a gene targeted mouse strain lacking the γchain which is necessary for development of T and NK cells. The mutant mice have a small amount of T and B cells, thus the mice were crossed with RAG-2 gene deficient mice to generate a new strain completely lacking T, B and NK cells. Both mouse strains lacking γchain gene alone and γchain plus RAG-2 genes have been back-crossed to C57BL/6 and Balb/c over 8 generations.
Using lymphocyte deficient C57BL/6 mice, we have studied xenograft transplantation of surgical specimens of human colorectal cancer (well or moderately differentiated adenocarcinoma) into subcutaneous pockets of the mice. Six speciman out of 7 have been alive in lympocyte defient mice as long as 2 to 6 months. Tumor cell invasion into a blood vessel or muscle layer was shown histologically. These results indicate that the severely immunocompomised mice provide environments for human colorectal cancer cells to live and grow invasively.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Ohtani K.: "Regulation of cell growth-dependent expression of mammalian CDC6 gene by cell cycle transcription factor E2F"Oncogene. 17. 1777-1785 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani K.: "Molecular mechanisms of promoter-regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T-cell leukemia virus type I"J. Biol. Chem.. 273. 14119-14129 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagata K.: "Selective expression of a novel G protein-coupled receptor by human T helper 2 cells,"J. Immunol.. 162. 1278-1286 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwanaga Y.: "Human T-cell leukemia virus type I Tax protein abrogates interleukin 2-dependence in a mouse T-cell line"J. Virol.. 73. 1271-1277 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani K.: "Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F"Oncogene. 18. 2299-2309 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohteki T.: "Interleukin-12 dependent interferon-γ production by CD8α^+ lymphoid dendric cells"J. Exp. Med.. 189. 1981-1986 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsukahara T.: "Induction of Bcl-X_L expression by HTLV-I Tax through NF-κB in apoptosis-resistant T-cell transformants with Tax"J. Virol.. 73. 7981-7987 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagata K.: "CRTH2, an orphan rceptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s)"FEBS Letters. 459. 195-199 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka K.: "Differential production of prostaglandin D2 by human helper T call subsets"J. Immunol.. (In press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani K.: "Cell type-specific E2F activation and cell cycle progression induced by the oncogene produc Tax of human T-cell leukemia virus type I"J. Biol. Chem.. (In press). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani, K., Tsujimoto, A., Tsukahara, T. Numata, N., Miura, S., Sugamura, K. & Nakamura, M.: "Molecular mechanisms of promoter regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T-cell leukemia virus type I."J. Biol. Chem.. 273. 14119-14129 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani, K., Tsujimoto, A., Ikeda, M. & Nakamura, M.: "Regulation of cell growth-dependent expression of mammalian CDC6 gene by cell cycle transcription factor E2F."Oncogene. 17. 1777-1785 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagata, K., Tanaka, K., Ogawa, K., Kemmotsu, K., Imai, T., Yoshie, O, Abe, H., Tada, K., Nakamura, M., sugamura, K. & Takano, S.: "Selective expression of a novel G protein-coupled receptor by human T helper 2 cells."J. Immunol.. 162. 1278-1286 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Iwanaga, Y., Tsukahara, T., Ohashi, T., Tanaka, Y., Arai, M., Nakamura, M., Ohtani, K., Koya, Y., Kannagi, M., Yamamoto, N. & fujii, M.: "Human T-cell leukemia virus type I Tax protein abrogates interleukin 2-dependence in a mouse T-cell line."J. Virol.. 73. 1271-1277 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani, K., Iwanaga, R., Nakamura, M., Ikeda, ., Yubata, N., Tsuruga, H. & Nojima, H.: "Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F."Oncogene. 18. 2299-2309 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohteki, T., fukao, T., Suzue, K., Maki, C., Ito, M., Nakamura, M. & Koyasu, S.: "Interleukin-12 dependent interferon-γ production by CD8αィイD1+ィエD1 lymphoid dendric cells."J. Exp. Med.. 189. 1981-1986 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tsukahara, T., Kannagi, M., Ohashi, T., Kato, H., Arai, M., Nunez, G., Iwanaga, Y., Yamamoto, N., Ohtani, K., Nakamura, M. & Fujii, M.: "Induction of Bcl-XィイD2LィエD2 expression by HTLV-I Tax through NF-κB in apoptosis-resistant T-cell transformants with Tax."J. Virol.. 73. 7981-7987 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nagata, K., Hirai, H., Tanaka, K., Ogawa, K., Aso, T., Sugamura, K., Nakamura, M. & Takano, S.: "CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s)."FEBS Letters. 459. 195-199 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka, K., Ogawa, K., Sugamura, K., Nakamura, M., Takano, S. & Nagata, K.: "Differential production of prostaglandin D2 by human helper T cell subsets."J. Immunol. (In press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani, K., Iwanaga, R., Arai, M., Huang, Y-P., Matsumura, Y. & Nakamura, M.: "Cell type-specific E2F activation and cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I."J. Biol. Chem.. (In press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ohtani, K.: "Regulation of cell growth-dependent expression of mammalian CDC6 gene by cell cycle transcription factor E2F."Oncogene. 17. 1777-1785 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohtani, K.: "Molecular mechanisms of promoter regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T-cell leukemia virus type I."J. Biol. Chem.. 273. 14119-14129 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagata, K.: "Selective expression of a novel G protein-coupled receptor by human T helper 2 cells."J. Immunol.. 162. 1278-1286 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Iwanaga, Y.: "Human T-cell leukemia virus type I Tax protein abrogates interleukin 2-dependence in a mouse T-cell line."J. Virol.. 73. 1271-1277 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohtani, K.: "Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F."Oncogene. 18. 2299-2309 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohteki, T.: "Interleukin-12 dependent interferon-γ production by CD8α^+ lymphoid dendric cells."J. Exp. Med.. 189. 1981-1986 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tsukahara, T.: "Induction of Bcl-X_L expression by HTLV-I Tax through NF-κB in apoptosis-resistant T-cell transformants with Tax."J. Virol.. 73. 7981-7987 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nagata, K.: "CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor (s)."FEBS Letters. 459. 195-199 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tanaka, K.: "Differential production of prostaglandin D2 by human helper T cell subsets."J. Immunol.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohtani, K.: "Cell type-specific E2F activation cell cycle progression by the oncogene product Tax of human T-cell leukemia virus type I."J. Biol. Chem.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohtani,K.: "Molecular mechanisms of promoter regulation of the gp34 gene that is trans-activated by an oncoprotein Tax of human T-cell leukemia virus type I." J.Biol.Chem.273. 14119-14129 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohtani,K.: "Regulation of cell growth-dependent expression of mammalian CDC6 gene by cell cycle transcription factor E2F." Oncogene. 17. 1777-1785 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagata,K.: "Selective expression of a novel G protein-coupled receptor by human T helper 2 cells." J.Immunol.162. 1278-1286 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iwanaga,Y.: "Human T-cell leukemia virus type I Tax protein has multiple distinct transforming activiteis in T-cells." J.Virol.73. 1271-1277 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohtani,K.: "Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F." Oncogene. (In press).

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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