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Development of efficient gene disruption system in any tissues or organs

Research Project

Project/Area Number 08557065
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Hematology
Research InstitutionOsaka University

Principal Investigator

TAKEDA Junji  Osaka University Medical School Professor, 医学部, 教授 (50163407)

Co-Investigator(Kenkyū-buntansha) SAKATA Tsuneaki  DNAVEC Research inc.Chief Researcher, 室長
NAKANISHI Mahito  Osaka University Research Institute for Microbial Deseases Assosiate Professor, 微生物病研究所, 助教授 (10172355)
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥16,100,000 (Direct Cost: ¥16,100,000)
Fiscal Year 1998: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1997: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 1996: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsCre / loxp / Hematopoietic stem cell / Tissue specific gene targeting / Pig-a / Pig-a / コンディショナルジーンターデッティング / 膜融合リポソーム / コンディショナルジーンターゲティング
Research Abstract

Gene disruption in murine embryonic stem (ES) cells allows to study functions of endogenous genes after establishing mice derived from targeted ES cells. Since many gene disruptions cause embryonic lethality, it is not possible to analyze specific gene functions in adult mice. To circumvent these difficulties, we applied Cre/loxP system. The system allows to disrupt a gene flanked by identically oriented loxP sites with Cre-expression-dependent manner.
In this study, we tried to apply two methods to introduce Cre recombinase into mouse genome, exogenous and endogenous way. For the former, liposome containing Gre was produced. Addition of the liposome to hematopoietic cells in vitro resulted in disruption of loxP containing gene (Pig-a). However, transfer of these cells into lethally irradiated mice revealed that Pig-a disruption did not occur in the hematopoietic stem cells. This result suggest that the exogenous Gre by the liposome has limitation to introduce Cre into the genome. For the latter, we established a series of Gre transgenic mice. Cre transgene worked very efficiently including hematopoietic stem cells.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Tarutani, M.: "Tissue-specific knockout of the mouse Pig-a gene reveals important roles for GPl-anchored proteins in skin development" Proc.Natl.Acad.Sci.94. 7400-7405 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeda, K.: "Stat3 Activation is Responsible for IL-6-Dependent T Cell Proliferation Through Preventing Apoptosis : Generation and Characterization of T Cell-Specific Stat3-Deficient Mice" J.Immunol.161. 4652-4660 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takahama, Y.: "Functional competence of T cells in the absence of GPl-anchored proteins caused by T-cell specific disruption of Pig-a gene." Eur.J.Immunol.28. 2159-2166 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nozaki, M.: "Developmental abnormalities of glycosylphosphatidylinositol-anchor deficient embryos revealed by Crc/oxP system" Lab.Invest.(1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tarutani, M., et al.: "Tissue specific knock-out-of the mouse Pig-a gene reveals important roles for GPI-anchored proteins in skin development." Proc.Natl.Acad.Sci.USA. 94. 7400-7405 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takahama, Y.et al.: "Functional competence of T cells in the absence of GPI-anchored proteins caused by T-cell specific disruption of Pig-a gene." Eur.J.Immunol. 28. 2159-2166 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takeda, K.et al.: "Stat3 activation is responsible for IL-6-dependent T cell proliferation through preventing characteraization of T cell specific stat3-deficient-mice." J.Immunol. 161. 4652-4660 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nozaki, M.et al.: "Developmental abnormalities of glycosylphosphatidylinositol-anchor deficient embryos revealed by Cre/loxP system" Lab.Invest.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takahama,Y.: "Functional competence of T cells in the absence of GP1-anchored proteins caused by T-cell specific disruption of Pig-a gene." Eur.J.Immunol.28. 2159-2166 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nozaki,M.: "Developmental abnormalities of glycosylphosphatidylinositol-anchor deficient embryos revealed by Cre/loxP system" Lab.Invest.(in press).

    • Related Report
      1998 Annual Research Report
  • [Publications] Nishimura,J.: "A patient with paroxysmal nocturnal hemoglobinuria bearing four independent PIG-A mutant clones." Blood. 89. 3470-3476 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tarutani,M.: "Tissue-specific knockout of the mouse Pig-a gene reveals important roles for GPI-anchored proteins in skin development." Proc.Natl.Acad.Sci.USA.94. 7400-7405 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Reika Watanabe et al.: "PIG-A and PIG-H,which participate in glycosyl phosphatidyl-inositol anchor biosynthesis,form a protein complex in the endoplasmic reticulum." Journal of Biological Chemistry. 271・43. 26868-26875 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Norimitsu Inoue et al.: "PIG-C,one of the three human genes involved in the first step of glycosylphosphatidylinositol biosynthesis is a homologue of Saccharomyces cerevisiae GPI2." Biochemical and Biophysical Research Communications. 226. 193-199 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Minoru Takahashi et al.: "PIG-B,a membrane protein of the endoplasmic reticulum with a large lumenal domain,is involved in transferring the third mannose of the GPI anchor." The EMBO Journal. 15・16. 4254-4261 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohishi,K.: "Cloning and characterization of the murine GPI anchor synthesis gene Pigf,a homologue of the human PIGF gene." Genomics. 34. 340-346 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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