1999 Fiscal Year Final Research Report Summary
Lymphocyte deficient mice as hosts for xenograft of human cells
| Project/Area Number |
10559007
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
広領域
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| Research Institution | Tokyo Medical and Dental University |
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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)
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| 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)
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| Project Period (FY) |
1998 – 1999
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| Keywords | immunodeficiency / animal model / common γchain / RAG1・RAG2 / knock-out mouse / human cancer |
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| 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.
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[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)
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[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)
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[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)
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[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)
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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