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GENE CONVERSION ASSOCIATED WITH HOMOLOGOUS RECOMBINATION AND DNA REPAIR OF THE MOUSE.

Research Project

Project/Area Number 05640699
Research Category

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

Allocation TypeSingle-year Grants
Research Field 遺伝
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

GONDO Yoichi  KYUSHU UNIVERSITY,MEDICAL INSTITUTE OF BIOREGULATION,ASSISTANT PROFESSOR, 生体防御医学研究所, 講師 (40225678)

Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywordshomologous recombination / DNA repair / gene conversion / mammal / molecular genetic / gene targeting / mouse genome / illegitimate recombination / ジーンターゲッティグ / 組換え修復 / ジーンターゲッテイング
Research Abstract

Mouse embryonic stem (ES) cell lines that carried a neo-tk cassette at the p53 locus on the chromosome 11 were established by nsing gene targeting. These ES cell lines for the first time provided a system to investigate the phenomena with respect to the homologous recombination of chromosomes. It has been demonstrated that the method encompassing two steps of gene targeting universally enabled to replace a gene with any DNA sequences. During the process of the development of this method, gene conversions were observed as clones of totally unexpected types of pseudo-homologous recombinants. Approximately 25% of the p53 gene-targeted clones were pseudo-homologous recombinants. In addition, the recombination repair has been also recognized between the wild-type (W) and targeted-type (T) alleles in theW/T heterozygote. This recombination repair occurred to either direction consistently. These achievements were already published (Gondo, et al., Biochem.Biophys.Res.Commun., 1994)
Three possib … More le models have been proposed for the molecular mechanism of the recombination repair. One is the gene conversion of the excision-repair type at the limited region of the p53 gene and its vicinities. The second feasible hypothesis is the mitotic recombination between the sister chromatids of the two homologues after S period of the cell cycle and subsequent segregation of the same alleles to the same daughter cells. The last model postulates no segregation of two sister chromatids of a homologue at mitosis resulting a gain of homozygosity of the entire chromosome as found in uniparental disomy. In order the examine the three working hypotheses, it is necessary to have a highly polymorphic ES cell line with molecular markers which allow us to distinguish those polymorphisms. Thus, one of such polymorphic ES cell line, TT2, was obtained from Dr.S.Aizawa (Kumamoto University). The TT2 ES cell line was established from a heterozygote of two inbred strains, CBA and C57BL/6. The gene targeting was performed again and 17 of the TT2 ES cell clones carrying the neotk cassette were newly established. The molecular markers on the chromosome 11 on which the p53 gene is were also investigated and 4 SSLP markers have been found so far to be polymorphic between CBA and C57BL/6.
By using this system, it became plausible to study the molecular mechanisms of the homologous recombination at a defined region of the chromosomes in the mammalian genome. More polymorphic markers on the chromosome 11 have been currently under investigation. Less

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Y.Gondo,et al.: "Gene replacement of the p53 gene with the lacZ gene in mouse embryonic stem cells and mice by using two steps of homologous recombination." Biochem. Biophys. Res. Commun.202. 830-837 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.H.Brilliant,et al.: "One-dimensional Genome Scanning:Identification of the basis of a mouse mutation and identification of genomic changes in ovarian carcinoma." Electrophoresis. 16. 163-167 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Gondo: "Size-selected genomic libraries:The distribution and size-fractionation of restricted genomic DNA fragments by gel electrophoresis." Electrophoresis. 16. 168-173 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Gondo and M.H.Brilliant: "Theoretical basis of one-dimensional genone scanning:A direct method to identify the site of a mutation." Electrophoresis. 16. 174-178 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 権藤洋一、他: "トランスジェニックマウスを用いた環境変異原検定系の開発" Environ.Mut.Res.Commun.16. 53-65 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 中村健司、他: "自在な遺伝子置換法" 実験医学. 11(20). 138-141 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 権藤洋一、他: "「疾患モデルマウス」標的遺伝子組換えの新しい戦略-自在な標的遺伝子置換法" 中山書店, 6 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 権藤洋一、他: "「疾患モデルマウス」HITECマウス:トランスジェニックマウスを用いた体細胞突然変異解析系" 中山書店, 5 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Gondo and M.H.Brilliant: "Theoretical Basis of One Dimensional Genome Scanning : A Direct Method to Identify the Site of a Mutation." Electrophoresis. 16. 174-178 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] M.H.Brillinant, Y.Gondo and A.Magliocco: "One-Dimensional Genome Scanning : Identification of the Basis of a Mouse Mutation and Identification of Genomic Changes in Ovarian Carcinoma." Electrophoresis. 16. 163-167 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Gondo : Size-Selected Genomic Libraries: "Distribution and Size-Fractionation of Restricted Genomic DNA Fragments by Gel Electrophoresis." Electrophoresis. 16. 168-173 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Gondo, K.Nakamura, K.Nakao, T.Sasaoka, K.Ito, M.Kimura and M.Katsuki: "Gene Replacement of the p53 gene with the lacZ gene in mouse embryonic stem cells and mice by using two steps of homologous recombination." Biochem, Biophys.Res.Commun. 202. 830-837 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Gondo, Y.Ikeda, Y.Motegi, M.Takahashi, A.Takeshita K.Nakao and M.Katsuki: "Development of new risk assessment test by using transgenic mice." Environ.Mut.Res.Commun. 16. 53-65 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] K.Nakamura, K.Nakao, Y.Gondo and M.Katsuki: "The universal gene replacement method in ES cells." Exp.Med. 11 (20). 138-141 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Y.Gondo,et al.: "Gene replacement of the p53 gene with the lacZ gene in mouse embryonic stem cells and mice by using two steps of homologous recombiration." Biochem.Biophys,Res.Commun.202. 830-837 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.H.Brilliant,et al.: "One-dimensional Genome Scanning:Identification of the basis of a mouse mutation and identification of Genomic changes in ovarian cavcinoma." Electrophoresis. 16. 163-167 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Gondo.: "Size-selected genomic libraries:The distribution and size-fractionation of restvicted genomic DNA fragments by gel electrophoresis." Electrophoresis. 16. 168-173 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Y.Gondo,et al: "Theoretical of one-dimensional genome scanning:A direct method to identify the site of a mutation." Electrophoresis. 16. 174-178 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 権藤洋一、他: "トランスジエニックマウスを用いた環境変異原検定系の開発" Environ.Mut.Res.Commun.16. 53-65 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 中村健司、他: "自在な標的遺伝子置換法" 実験医学. 11(20). 138-141 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 権藤洋一、他: "「疾患モデルマウス」標的遺伝子組換えの新しい戦略-自在な標的遺伝子置換法" 中山書店, 6 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 権藤洋一、他: "「疾患モデルマウス」HITECマウス:トランスジェニックマウスを用いた体細胞突然変異解析系" 中山書店, 5 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] M.H.Brilliant: "Direct molecular identification of the mouse pink-eyed unstable mutation by genome scanning" Science. 252. 566-569 (1991)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Nakatsu: "The p_-locus is closly linked to the mouse homdog of a gene from the Prader-Willi chromosome region." Mammalian Genome. 2. 69-71 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.H.Brilliant: "Molecular characterization of the P^<un>_-allele of the mouse pink-eyed dilution locus." Pigment Cell Research. 5. 271-273 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] J.M.Gardner: "The mouse pink-eyed dilution gene:Association with human Prader-Willi and Angelman syndromes." Science. 257. 1121-1124 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.F.Lyon: "Genetic and molecular analysis of recessive alleles at the pink-eyed dilution (p_-)locus of the mouse." Proc.Natl Acad.Sci.USA. 89. 6968-6972 (1992)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Gondo: "High-frequency genetic reversion mediated by a DNA duplication:Mouse pink-eyed unstablemutation" Proc.Natl.Acad.Sci.USA. 90. 297-301 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 権藤洋一: "トランスジェニックマウスを用いた変異原の高感度解析法の開発" 環境変異原研究. 15. 39-49 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 中村健司: "自在な標的遺伝子置換法" 実験医学. 11(20). 138-141 (1993)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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