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Functional redundancy of the three ras genes which uses ras genes knock-out mice.

Research Project

Project/Area Number 10670193
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionThe University of Tokyo

Principal Investigator

NAKAMURA Kenji  The Institute of Medical Science The University of Tokyo, Research Associate, 医科学研究所, 助手 (90253533)

Co-Investigator(Kenkyū-buntansha) NAKAO Kazuki  The Institute of Medical Science The University of Tokyo, Research Associate, 医科学研究所, 寄付研究部門教員 (20217657)
AIBA Atsu  The Institute of Medical Science The University of Tokyo, Associate Professor, 医科学研究所, 助教授 (20271116)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsK-ras / H-ras / N-ras / gene replacement / ES cells / gene targeting / knock-out mice / mouse
Research Abstract

In mammals, three ras genes, H-ras, N-ras and K-ras encode homologous but distinct 21-kDa Ras proteins. No clear evidence for the individual in vivo functions of each ras gene and functional redundancy of the three ras genes has yet been reported. We herein show the functional redundancy of the three ras genes, H-ras, N-ras and K-ras, by investigating the phenotypes of mice deficient in each of these genes, mice deficient in multiple ras genes and H-ras transgenic mice. H-ras-/- mice and N-ras-/- mice as well as a substantial proportion of H-ras-/- N-ras-/- mice that express only the K-ras gene are viable, while K-ras-/- mice have been previously shown to be embryonically lethal. An investigation of neonatal death of N-ras-/- K-ras+/- and H-ras-/- N-ras-/- mice has shown that a part of these mice died because of chylous ascites and intestinal lymphedema. Most ras mutant mice lacking 2 or more ras alleles exhibited a similar phenotype. The incidence of intestinal lymphedema increases as the number of null alleles of any three ras genes increase, which thus suggests that the function of three ras genes is redundant. To prove this hypothesis, we introduce the human H-ras transgenes into single and multiple ras mutant mice and found the H-ras transgenes to rescue all abnormalities exhibited in the development of these ras mutant mice. We therefore conclude that the function of the ras genes is redundant in vivo.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Sunahara, S., et al.: "The oocyte-specific methylated region of the U2afbp-rs/U2afl-rsl gene is dispensable for its imprinted methylation."Biochem Biophys Res Commun. 16. 590-595 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tamura, N., et al.: "Cardiac fibrosis in mice lacking brain natriuretic peptide."Proc Natl Acad Sci USA. 97. 4239-4244 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ise, K., et al.: "Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis."Oncogene. 19. 2951-2956 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato, T., et al.: "Transgenic mice harboring a full-length human mutand DRPLA gene exhibit age-dependent intergenerational and somatic instabilities of CAG repeats comparable with those in DRPLA patients."Human Molecular Genetics. 8. 99-106 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Naito, A., et al.: "Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice."Gene to Cells. 4. 353-362 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sugiyama, T., et al.: "Localization of phospholipase Cbeta isozymes in the mouse cerebellum."Biochem Biophys Res Commun. 19. 473-478 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato, T., et al.: "Transgenic mice harboring a full-length human DRPLA gene with highly expanded CAG repeats exhibit severe disease phenotype."American Journal of Human Genetics. 65. 154-154 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honda, H., et al.: "Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas."Nat Genet. 19. 361-365 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikawa, H., et al.: "Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses."Gene to Cells. 3. 685-695 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sugihara, K., et al.: "Rac1 is required for the formation of three germ layers during gastrulation."Oncogene. 17. 3427-3433 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sunahara, S., et al.: "The oocyte-specific methylated region of the U2afbp-rs/U2af1-rs1 gene is dispensable for its imprinted methylation."Biochem Biophys Res Commun. 16. 590-595 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tamura, N., et al.: "Cardiac fibrosis in mice lacking brain natriuretic peptide."Proc Natl Acad Sci USA. 97. 4239-4244 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ise, K., et al.: "Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis."Oncogene. 19. 2951-2956 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato, T., et al.: "Transgenic mice harboring a full-length human mutant DRPLA gene exhibit age-dependent intergenerational and somatic instabilities of CAG repeats comparable with those in DRPLA patients."Human Molecular Genetics. 8. 99-106 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Naito, A., et al.: "Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice."Gene to Cells. 4. 353-362 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sugiyama, T., et al.: "Localization of phospholipase Cbeta isozymes in the mouse cerebellum."Biochem Biophys Res Commun. 19. 473-478 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato, T., et al.: "Transgenic mice harboring a full-length human DRPLA gene with highly expanded CAG repeats exhibit severe disease phenotype."American Journal of Human Genetics. 65. 154-154 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honda, H., et al.: "Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas."Nat Genet. 19. 361-365 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yoshikawa, H., et al.: "Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses."Gene to Cells. 3. 685-695 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sugihara, K., et al.: "Rac1 is required for the formation of three germ layers during gastrulation."Oncogene. 17. 3427-3433 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sunahara,S., et al.: "The oocyte-specific methylated region of the U2afbp-rs/U2af1-rs1 gene is dispensable for its imprinted methylation."Biochem Biophys Res Commun. 16. 590-595 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tamura,N., et al.: "Cardiac fibrosis in mice lacking brain natriuretic peptide."Proc Natl Acad Sci USA. 97. 4239-4244 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ise,K., et al.: "Targeted deletion of the H-ras gene decreases tumor formation in mouse skin carcinogenesis."Oncogene. 19. 2951-2956 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sato,T., et al.: "Transgenic mice harboring a full-length human mutant DRPLA gene exhibit age-dependent intergenerational and somatic instabilities of CAG repeats comparable with those in DRPLA patients."Human Molecular Genetics. 8. 99-106 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Naito,A., et al.: "Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice."Gene to Cells. 4. 353-362 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sugiyama, T., et al.: "Localization of phospholipase Cbeta isozymes in the mouse cerebellum"Biochem Biophys Res Commun. 19. 473-478 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sato,T., et al.: "Transgenic mice harboring a full-length human DRPLA gene with highly expanded CAG repeats exhibit severe disease phenotype."American Journal of Human Genetics. 65. 154-154 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sunahara, S., et al.: "The oocyte-specific methylated region of the U2afbp-rs/U2af1-rs1 gene is dispensable for its imprinted methylation"Biochem Biophys Res Commun. 16. 590-595 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Honda,H.,et al.: "Cardiovascular anomaly,impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas." Nat Genet. 19. 361-365 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshikawa,H.,et al.: "Mice lacking smooth muscle calponin display increased bone formation that is associated with enhancement of bone morphogenetic protein responses." Gene to Cells. 3. 685-695 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sugihara,K.,et al.: "Rac1 is required for the formation of three germ layers during gastrulation." Oncogene. 17. 3427-3433 (1998)

    • Related Report
      1998 Annual Research Report

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

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