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Knock-down mouse, a novel gene engineering mouse for use as a disease model

Research Project

Project/Area Number 11480251
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory animal science
Research InstitutionCentral Institute for Experimental Animals

Principal Investigator

OHNISHI Yasuyuki  Central Institute for Experimental Animals Lab.Oncology Head, 腫瘍研究室, 室長 (70201382)

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)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2000: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1999: ¥10,100,000 (Direct Cost: ¥10,100,000)
Keywordsribozyme / mouse / insulin / vascular endotherial growth factor / xenotransplantability / K-ras / human neoplasm / tetracyclin / スイッチ / トランスジェニック
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.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Oshika,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(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tokunaga,T.: "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(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tsuvhida,T: "Adenovirus-mediated anti-h-ras ribozyme induces apoptosis and growth suppression of human pancreatic carcinoma"Caccer Gene Therapy. 7. 373-383 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takakura, A., Ohnishi, Y., Itoh, T., Yoshimura M., Urano, K.and Ueyama, Y.: "Decontamination of human xenotransplantable tumor with mouse hepatitis virus by implantation in nude rat : A case report."Exp.Anim.. 49. 39-41 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [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
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Oshika,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)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tokunaga,T.: "Ribozyme-mediated inactivation of mutant K-ras oncogene in a colon cancer cell line"Br.J.Cancer. 83. 833-839 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueyama T.: "In vivo chemosensitivity of human malignant cystosarcoma phyllodes xenograft"Oncol.Rep.. 7. 257-260 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takakura A.: "Decontamination of human xenotransplantable tumor with mouse hepatites virus by implantation in nude rat : A case report"Experimental Animals. 49. 39-41 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okamoto K.: "Xenografts of solid tumors frequently express cellular-associated isoform of vascular endothelial growth factor (VEGF) 189"Oncol.Rep.. 6. 553-556 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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