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STUDIES ON THE MECHANISM OF SOMATIC MUTATION OF IMMUNOGLOBLIN GENES USING TRANSGENIC MICE.

Research Project

Project/Area Number 04454211
Research Category

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

Allocation TypeSingle-year Grants
Research Field Immunology
Research InstitutionNAGOYA CITY UNIVERSITY SCHOOL OF MEDICINE

Principal Investigator

AZUMA Takachika  NAGOYA CITY UNIV.SCH.MED., Associate prof., 医学部, 助教授 (00028234)

Co-Investigator(Kenkyū-buntansha) OKADA Hidechika  NAGOYA CITY UNIV.SCH.MED., Prof., 医学部, 教授 (30160683)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1993: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1992: ¥5,200,000 (Direct Cost: ¥5,200,000)
KeywordsImmunoglobulin / Somatic mutation / Transgenic mouse / 抗体 / トランスジェニック
Research Abstract

Transgenic mice containing the chloramphenicol acetyl transferase (CAT) gene driven by the immunoglobulin (Ig) V_H promoter and the heavy chain intron enhancer were prepared to increase our ounderstanding of the mechanism responsible for somatic mutation. Hybridomas were prepared after multiple immunization of a transgenic mouse with a thymus dependent antigen. We analyzed mutations in the CAT coding region as well as in the region 5' upstream of the promoter after amplification of DNA using PCR followed by sequencing of cloned DNA.The results of DNA sequencing suggested that mutation occurred only in the CAT gene but not in the promoter or enhancer. The rate of mutetion in the CAT gene was estimated to be 1.6X10^<-5> per base pair per cell division, which was lower limit of the rate for somatic mutation reported for Ig genes. These results suggested that the mutator mechanism can operate in a non-Ig gene provided it is flanked by the V_H promoter and heavy chain intron enhancer.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] N.Motoyama: "Comparison of somatic mutation frequency among immunoglobulin genes" J.Exp.Med.179. 395-403 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] T.Azuma: "Mutations of the chloramphenicol acetyl transferase transgene driven by the immunoglobulin promoter and intron enhancer" Int.Immunol.5. 121-130 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] R.Wolf-Levin: "Specific IgG autoantibodies are potent inhibitors of autoreactive T cell response to phytohemaggglutinin-activated T cells" J.Immunol.151. 5864-5877 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Motoyama: "Comparison of somatic mutation frequency among immunoglobulin genes" J.Exp.Med.179. 395-403 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] T.Azuma: "Mutation of the chloramphenicol acetyl transferase transgene driven by immunoglobulin promoter and intron enhancer." Int.Immunol.5. 121-130 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] R.Wolf-Levin: "Specific IgG autoantibodies are potent inhibitors of autoreactive T cell response to phytohemagglutinin-activated T cells." J.Immunol.151. 5864-5877 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Motoyama,T.Miwa,Y.Suzuki T.AZUMA H.Okada: "Comparison of Somatic Mutation Freguency among Immunoglsbulin" J.Exp.Med.179. 395-403 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] R.Wolf-Levin,T.Azuma,K.Aoki Y.Yagami,H.Okada: "Specific IgG Autoantibodies Are Potent Inhibitors of Autoreactive T cell Response to Phytohemagglutimin-Activated T cells." J.Immunol.151. 5864-5877 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] H.Okada,H.Momota,N.Okada,T.Okamoto,T.Azuma: "Elimination of HIV-infected cells by lymphocytes armed with a bifunctional antibody to gp120 of HIV and CD3" Immunology letters. 38. 195-199 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] TAKACHIKA AZUMA,Noboru MOTOYAMA,LARRY E.FIELDS,DENNIS Y.LOH: "Mutation of the chloramphenicol acetyl transferase transgene driven by the immunoglobulin promoter and intron enhancer." International Immunology. 5. 121-130 (1993)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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