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Elucidation of mechanism for fixation of mutations occurred in germ cells using medaka.

Research Project

Project/Area Number 11236204
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

FUKAMACHI Shoji (2003)  The University of Tokyo, Graduate School of Frontier Sciences, Research Associate, 大学院・新領域創成科学研究科, 助手 (20323446)

嶋 昭紘 (1999-2002)  東京大学, 大学院・新領域創成科学研究科, 教授 (60011590)

Co-Investigator(Kenkyū-buntansha) SHIMA Akihiro  The University of Tokyo, Graduate School of Frontier Sciences, Professor Emeritus, 大学院・新領域創成科学研究科, 名誉教授 (60011590)
Project Period (FY) 1999 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥93,200,000 (Direct Cost: ¥93,200,000)
Fiscal Year 2003: ¥21,300,000 (Direct Cost: ¥21,300,000)
Fiscal Year 2002: ¥21,300,000 (Direct Cost: ¥21,300,000)
Fiscal Year 2001: ¥23,900,000 (Direct Cost: ¥23,900,000)
Fiscal Year 2000: ¥7,900,000 (Direct Cost: ¥7,900,000)
Fiscal Year 1999: ¥18,800,000 (Direct Cost: ¥18,800,000)
Keywordscells / medaka / mechanism for maintaining of genome stability / apoptosis / p53 / 自然突然変異 / 色素細胞 / ポジショナルクローニング / γ-rays / Medaka fish / Speruatogenesis / MBT / Expression of paternal genome / Polymorphism / 生殖細胞突然変異 / 特定座位法 / 自然突然変異率 / 精原細胞 / 細胞死 / P53 / ESTマーカー / 父性発現 / TUNEL陽性細胞 / チェックポイント / p53遺伝子 / ATM遺伝子 / メダカ生殖細胞突然変異 / 雄生殖細胞 / 精原幹細胞 / 分化型精原細胞 / 高感受性集団 / 低線量 / 胚死
Research Abstract

Germ-cell mutations caused in an organism are the source of genetic variation that is required for evolution, but at the same time, they may accumulate deleterious traits within a species. We have measured spontaneous germ-cell mutation rate at the pigmentation loci of the Medaka The resulting value was about 8×10^<-6>/locus/generation, indicating that vertebrate species share a common level of germ-cell mutation rate. Based on g-irradiation study, apoptosis of early differentiating spermatogonia with DNA damage proved to have an important role for regulation of overall mutation rate in male germ cells. In contrast mutation rate in female germ cells appeared to depend on fidelity of DNA repair. Next we found that spontaneous chromosomal breakages. and deletions are frequently caused in female germ cells of the Niigata wild population. Detailed analyses suggested that a novel mechanism for genome arrangement is involved in induction of germ-cell mutations in the wild populations of the Medaka Furthermore, we analysed the spectrum of spontaneous mutations by identifying spontaneous body-colour mutants. We positionally cloned responsible genes for the b, ci and i-3 mutants and identified they are caused by inversion, duplication or deletion of from several to dozens of nucleotides. Though others reported only insertions of transposon-like elements as a cause of spontaneous mutations on medaka genes (i, el, and rs-3), it is proved that that is not only the case. Meanwhile, because we isolated three pigmentation genes (functions of two of them are newly revealed by this study), we could provide new insights for developmental and evolutional studies of pigment cells.

Report

(6 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] Naruse K.: "A Detailed Linkage Map of Medaka, Oryzias latipes. Comparative genomics and genome evolution."Genetics.. 154. 1773-1784 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kondo S: "The medaka rs-3 locus required for scale development encodes ectodysplasin-A receptor."Current Biology. 11. 1202-1206 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kondo M.: "Differences in recombination frequencies during female and male meioses of the sex chromosomes of the medaka, Oryzias latipes."Genet.Research. 78. 23-30 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okubo K.: "Identification and Characterization of Two Distinct GnRH Receptor Subtypes in a Teleost, the Medaka Orvzias latipes."Endocrinology. 142. 4729-4739 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimada, A.: "High incidence of mosaic mutations induced by irradiating paternal germ cells of the medaka fish, Oryzias latipes."Mutation Research. 495. 33-42 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukamachi, S.: "Genomic analysis of gamma-ray-induced germ-cell mutations at the b locus recovered from the medaka specific-locus test."Mutati on Res earth. 458. 19-29 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukamachi, S.: "Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka."Nature Genetics. 28. 381-385 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuwahara, Y.: "A critical stage in spermatogenesis for radiation-induced cell death in the medaka fish, Oryzias latipes"Radiation Research. 157. 386-392 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakayama, K.: "Distinctive distribution of AIMl polymorphism among major human populations with different skin color."Journal of Human Genetics. 47. 92-94 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimada, A.: "Induction and characterization of mutations at the b locus of the medaka, Oryzias latipes."Zoological Science. 19. 411-417 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wittbrodt, J.: "Medaka - A model organism from the Far East."Nature Reviews Genetics. 3. 53-64 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shima, A.: "Fish genomes flying - Symposium on Medaka genomics."EMBO reports. 4. 121-125 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Aizawa, K.: "The medaka midblastula transition as revealed by the expression of the paternal genome."Gene Expression Patterns. 3. 43-47 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuwahara, Y.: "Gamma-ray exposure accelerates spermatogenesis of medaka fish, Oryzias latipes."Molecular Reproduction and Development. 65. 204-211 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Naruse K., Fukamachi S., Mitani H., Kondo M., Matsuoka T., Kondo S., Hanamura N., Moritia Y., Hasegawa K., Nishigaki R., Shimada A., Wada H., Kusakabe T., Suzuki N., Kinoshita M., Kanamori A., Terado T., Kimura H., Nonaka M., Shima A.: "A Detailed Linkage Map of Medaka, Oryzias latipes. Comparative genomics and genome evolution."Geneti cs.. 154. 1773-1784 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kondo S, Kuwahara Y., Kondo M., Naruse K., Mitani H., Wakamatsu Y., Ozato K., Asakawa S., Shimizu N., Shima, A.: "The medaka rs-3 locus required for scale development encodes ectodysplasin-a receptor."Current Biology. 11. 1202-1206 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kondo M., Nagao E., Mitani H., Shima A.: "Differences in recombination frequencies during female and male meioses of the sex chromosomes of the medaka, Oryzias latipes."Genet. Res.. 78. 23-30 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Okubo K., Nagata S., Ko R., Kataoka H., Yoshiura Y., Mitani, H., Kondo M., Naruse K., Shima A., Aida, K.: "Identification and Characterization of Two Distinct GnRH Receptor Subtypes in a Teleost, the Medaka Oryzias latipes."Endocrinology. 142. 4729-4739 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimada, A., Shima, A.: "High incidence of mosaic mutations induced by irradiating paternal germ cells of the medaka fish, Oryzias latipes."Mutation Research. 495. 33-42 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukamachi, S.Shimada, A., Naruse, K., Shima A.: "Genomic analysis of gamma-ray-induced germ-cell mutations at the b locus recovered from the medaka specific-locus test."Mutation Research. 458. 19-29 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukamachi, S., Shimada, A., Shima, A.: "Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka."Nature Genetics. 28. 381-385 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuwahara Y., Shimada, A., Mitani, H., Shima, A.: "A critical stage in spermatogenesis for radiation-induced cell death in the medaka fish, Oryzias latipes."Radiation Research. 157. 386-392 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakayama, K., Fukamachi, S., Kimura, H., Koda, Y., Soemantri, A., Ishida, T.: "Distinctive distribution of AIM1 polymorphism among major human populations with different skin color."Journal of Human Genetics. 47. 92-94 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shimada, A., Fukamachi, S., Wakamatsu, Y., Ozato, K., Shima, A.: "Induction and characterization of mutations at the b locus of the medaka, Oryzias latipes."Zoological Science. 19. 411-417 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wittbrodt, J., Shima, A., Schartl, M.Medaka: "A model organism from the Far East."Nature Reviews Genetics. 3. 53-64 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shima, A., Himmelbauer, H., Mitani, H., Furutani-Seiki, M., Wittbrodt, J., Schartl, M.: "Fish genomes flying-Sympsoium on Medaka genomics."EMBO reports. 4. 121-125 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Aizawa, K., Shimada, A., Naruse, K., Mitani, H., Shima, A.: "The medaka midblastula transition as revealed by the expression of the paternal genome."Gene Expression Patterns. 3. 43-47 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuwahara, Y., Shimada, A., Mitani, H., Shima, A.: "Gamma-ray exposure accelerates spermatogenesis of medaka fish, Oryzias"Molecular Reproduction and Development. 65. 204-211 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuwahara Y, Shimada A, Mitani H, Shima A.: "Gamma-ray exposure accelerates spermatogenesis of medaka fish, Oryzias latipes"Molecular Reproduction and Development. 65・2. 204-211 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shima A, Himmelbauer H, Mitani H, Furutani-Seiki M, Wittbrodt J, Schartl M.: "Fish genomes flying. Symposium on Medaka Genomics"EMBO Reports. 4・2. 121-125 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Aizawa K, Shimada A, Naruse K, Mitani H, Shima A.: "The medaka midblastula transition as revealed by the expression of the paternal genome"Gene Expression Patterns. 3・1. 43-47 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kuwahara Y, Shimada A, Mitani H, Shima A.: "γ-ray accelerates the spermatogenesis of the Medaka fish, Oryzias l atipes"Molecular Reproduction and Development. (In press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Aizawa K, Shimada A, Naruse K, Mitani H, Shima A: "The medaka midblastula transition as revealed by the expression of the paternal genome"Gene Expression Patterns. 3. 43-47 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kuwahara Y, Shimada A, Mitani H, Shima A: "A critical stage in spermatogenesis for radiation -induced cell death in th e medaka fish, Oryzias latipes"Radiation Research. 157. 386-392 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 桑原義和, 島田敦子, 三谷啓志, 嶋昭紘: "総説 メダカ雄生殖細胞におけるゲノム損傷排除機構としてのアポトーシス"放射線生物研究. 37. 158-168 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukamachi, S., Shimada, A., Shima, A.: "Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka"Nature Genetics. 28. 381-385 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shimada, A., Shima, A.: "High incidence of mosaic mutations induced by irradiating germ cells of the Medaka fish, Oryzias latipes"Mutation Research. 495. 33-42 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukamachi, S., Shimada, A., Naruse, K., Shima, A.: "Genomic analysis of gamma-ray induced germ cell mutations at the b-locus recovered from the medaka specific-locus test"Mutation Research. 458. 19-29 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kuwahara, Y., Shimada, A., Mitani, H., Shima A.: "A critical stage in spermatogenesis for radiation-induced cell death in the medaka fish, Oryzias latipes"Radiation Research. (in press). (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shima, A., Shimada, A.: "The Medaka as a model for studying germ-cell mutagenesis and genomic instability"Marine Biotecnology. 3. S162-S167 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 島田敦子,嶋昭紘: "メダカにおける自然および誘発生殖細胞突然変異率とその系統差"蛋白質,核酸,酵素. 45巻. 2886-2892 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukamachi,S.,Shimada,A. & Shima,A.: "Genomic analysis of gamma-ray-induced germ cell mutations at the b-locus recovered feom the Medaka SLT."Mutation research. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sun, H. et al.: "Evolutionary analysis of putative olfactory receptor"Gene. 231. 137-145 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Naruse, K. et al.: "A detailed linkage map of Medaka, Oryzias latipes :"Genetics. (in press). (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2018-03-28  

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