2000 Fiscal Year Final Research Report Summary
Knock-down mouse, a novel gene engineering mouse for use as a disease model
| Project/Area Number |
11480251
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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 | 一般 |
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| Research Field |
Laboratory animal science
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| Research Institution | Central Institute for Experimental Animals |
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Principal Investigator |
OHNISHI Yasuyuki Central Institute for Experimental Animals Lab.Oncology Head, 腫瘍研究室, 室長 (70201382)
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| Co-Investigator(Kenkyū-buntansha) |
UEYAMA Yoshito Tokai Univ.Sch.Med. Dept.Pathol. Associate Prof., 病態診断系病理学, 助教授 (30072408)
KURAMOCHI Takashi Central Institute for Experimental Animals Animal Resource Ctr. Research, 動物資源センター, 研究員 (10225253)
MIZUSHIMA Tomoko Cent.Inst.Exp.Anim. Lab.Oncology Research, 腫瘍研究室, 研究員 (90311240)
鬼島 宏 東海大学医学部, 病態診断系病理学, 講師 (90204859)
NAKAMURA Masato Tokai Univ.Sch.Med. Dept.Pathol. Instractor (00164335)
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| Project Period (FY) |
1999 – 2000
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| Keywords | ribozyme / mouse / insulin / vascular endotherial growth factor / xenotransplantability / K-ras / human neoplasm / tetracyclin |
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| Research Abstract |
In this research, we attempt to create a novel gene engineering mouse which contains the target gene expression-switch such as tetracycline regulated gene expression system (Tet-OFF and Tet-ON) and a gene for ribizyme driven by the switch system. First, we constructed an anti-insulin ribozyme, and examined in vitro cleaving assay using synthesized insulin RNA and the ribozyme. The ribozyme showed in vitro cleavage activity to the RNA.The ribozyme also showed anti-insulin activity in M6 insulinoma cell transfectant system. Another ribozymes were created for VEGF (vascular endotherial growth factor) and activated K-ras gene RNA, and they showed cleaving activity in cell transformant and in vitro cleavage assay system.
Also, tumor cells transfected by the anti-VEGF or anti-K-ras ribozyme showed reduced tumorigenic activity in nude mouse. Transgenic mice for rusiferase gene driven by the Tet-OFF and Tet-ON system were created. The mice were under exanimation.
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Research Products
(13 results)
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[Publications] Maruyama, C., Tomisawa, M., Wakana, S., Yamazaki, H., Kijima, H., Suemizu, H., Ohnishi, Y., Urano, K., Usui, T., Nakamura, M., Tsuchida, T., Mitsumori, K., Nomura, T., Tamaoki, N., and Ueyama, Y.: "Overexpression of human H-ras transgene is responsible for tumors induced by chemical carcinogens in mice."Oncol.Rep.. 8. 233-237 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ohnishi, Y., Arai, T., Koshirakawa, M., Horii, N., Nakajo, S., Urano, K., Usui, T., Tamaoki, N., and Ueyama, Y.: "Induction of drug metabolism-related enzymes by methylcholanthrene and phenobarbital in transgenic mice carrieng human prototype c-Ha-ras gene and their wild type littermates."Exp.Anim.. 50. 33-39 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Chulan, S., Yamato, T., Furukawa, T., Ohnishi, Y., Kijima, H.and Horii, A.: "Characterization of the mutations of the K-ras, p53, p16, and SMAD4 genes in 15 human pancreatic cancer cell lines."Oncol.Rep.. 8. 89-92 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Oshika, Y., Nakamura, N., Tokunaga, T., Ohnishi, Y., Abe, Y., Tsuchida, T., Tomii, Y., Kijima, H., Yamazaki, H., Ozeki, Y., Tamaoki, N., and Ueyama, Y.: "Ribozyme approach to downregulate vascular endothelial growth factor (VEGF) 189 expression in non-small cell lung cancer (NSCLC)"Eur.J.Cancer. 36. 2390-2396 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Tokunaga, T., Tsuchida, T., Kijim, H., Okamoto, K., Ohnishi, Y., Yamazaki, H., Miura, S., Ueyama, Y.and Nakamura, M.: "Ribozyme-mediated inactivation of mutant K-ras oncogene in a colon cancer cell line."Br.J.Cancer. 83. 833-839 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Ueyama, Y., Abe, Y., Ohnishi, Y., Sawa, N., Hatanaka, H., Handa, A., Tokuda, Y., Yamazaki, H., Kijima, H., Tamaoki, N.and Nakamura, M.: "In vivo chemosensitivity of human malignant cystosarcoma phyllodes xenograft."Oncol.Rep.. 7. 257-260 (2000)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Okamoto, K., Oshika, K., Fukushima, Y., Ohnishi, Y., Tokunaga, T., Tomii, Y., Kijima, H., Yamazaki H., Ueyama, Y., Tamaoki, N.and Nakamura, M.: "Xenografts of solid tumors frequently express cellular-associated isoform of vascular endothelial growth factor (VEGF) 189."Oncol.Rep.. 6. 1201-1204 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Okamoto, K., Oshika, K., Fukushima, Y., Yoshimura, M., Ohnishi, Y., Tokunaga, T., Hashimoto, T., Hatanaka, H., Tomii, Y., Yoshida, Y., Miura, S., Tsuchida, T., Kijima, H., Yamazaki, H., Nakamura, M.and Ueyama, Y.: "Inhibition of liver metastasis of colon cancer by in vivo administration of anti-vascular endothelial growth factor antibody."Oncol.Rep.. 6. 553-556 (1999)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Masuda, K., Kijima, H., Kim., HM., Han, SB., Ohnishi, Y., Sawa, N., Oshika, Y., Tokunaga, T., Tsuchida, T., Abe, Y., Hamana, T., Matsubayashi, H., Yamazaki, H., Tamaoki, N., Ueyama, Y.and Nakamura, M.: "Heterozygous ras mutations are preserved in serially passaged human tumor xenografts and established cell lines."Oncol.Rep.. 6. 741-745 (1999)
Description
「研究成果報告書概要(欧文)」より
