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Mechanism for Developmental Regulation by Genomic Imprinting in the Female Germ Line.

Research Project

Project/Area Number 11234205
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo University of Agriculture

Principal Investigator

KONO Tomohiro  Faculty of Applied Bioscience, Professor, 応用生物化学部, 教授 (80153485)

Co-Investigator(Kenkyū-buntansha) OBATA Yayoi  Gene Research Centre, Gunma University, Assistant, 遺伝子実験施設, 助手 (70312907)
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥55,200,000 (Direct Cost: ¥55,200,000)
Fiscal Year 2002: ¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2001: ¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2000: ¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 1999: ¥14,400,000 (Direct Cost: ¥14,400,000)
KeywordsGenomic imprinting / Oocytes / Parthenogenesis / Gene expression / DNA methylation / Nuclear transfer / 発生・分化 / 発現制御 / 生殖細胞 / 哺乳動物 / ゲノムインプリント / 胚発生 / マウス
Research Abstract

In mammals, epigenetic modification of genomes during gametogenesis leads to an unequivalent expression of imprinted genes between parental alleles and necessary for term development. To understand the further insight into genomic imprinting we have done several lines of experiment. Firstly, to investigate when and how, precisely, maternal primary imprinting is established, we produced parthenogenetic embryos containing one genome from a non-growing or growth stage oocyte from 1- to 20-day old mice, and one from a fully-grown oocyte from adult mice. Using these embryos, expression analysis of eight imprinted genes, Snrpn, Znfl27, Ndn, Peg3, Igf2r, p57^<KIP2>, Peg1 and Impact, was conducted. The results show that the epigenetic markers for each imprinted gene are not imposed all together at a specific time during oocyte growth, but rather occurs within a wide range during the period from primary to antral follicle stage oocytes. The developmental ability of the constructed parthenogenet … More ic embryos is gradually reduced with the growth of nuclear donor oocytes. Thus, the present study clearly demonstrate that maternal primary imprinting occurs in a stepwise fashion for groups of imprinted genes during the oocyte growth stages. Secondly, we examined whether the regulation of H19 monoallelic expression enhances the survival of parthenogenetic embryos. The results clearly show that the ng/fg parthenogenetic embryos carrying the ng-oocyte genome that had been deleted by the H19 transcription unit successfully developed as live fetuses for 17.5 gestation days. Control experiments revealed that this unique phenomenon occurs irrespective of the genetic background effect. Histological analysis showed that the placenta of ng^<H19-KO>/fg^<WT> parthenotes was resulted in atrophia with sever negro-cytosis and other anomalies. The present results suggest that the cessation of H19 gene expression from the ng-allele causes the extended development and that functional defection of the placenta could be fatal for the ontogeny. Less

Report

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

    (67 results)

All Other

All Publications (67 results)

  • [Publications] Bao, S., Ushijima, H., Hirose, A., Fumihito, A., Ono, Y., Kono, T.: "Development of bovine oocytes reconstructed with a nucleus from growing stage oocytes after fertilization in vitro"Theriogenology. 59. 1231-1239 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimozawa, N., Ono, Y., Kimoto, S., Hioki, K., Araki, Y., Shinkai, Y., Kono, T., Ito, M.: "Abnormalities in cloned mice are not transmitted to the progeny"Genesis. 34. 203-207 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Obata, Y., Kono, T., Hatada, I.: "Maturation of mouse fetal germ cells in vitro"Nature. 418. 497-498 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimozawa, N.,, Muguruma, K., Hioki, K., Arai, Y., Kono, T., Ito, M.: "Direct production of gene-targeted mice from ES cells by nuclear transfer and gene transmission to their progeny"Exp. Anim.. 51. 375-381 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Bao, S., Obata, Y., Ono, Y., Futatsumata, N., Niimura, S., Kono, T.: "Nuclear competence for maturation and pronuclear formation in mouse oocytes"Human Reprod.. 17. 1311-1316 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sotomaru, Y., Katsuzawa, Y., Hatada, I., Obata, Y., Sasaki, H., Kono, T.: "Unregulated expression of the imprinted genes H19 and lgf2r in mouse uniparental fetuses"J. Blot. Chem.. 277. 12474-12478 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimoda, M., Morita, S., Obata, Y., Sotomaru, Y., Kono, T., Hatada, I.: "Imprinting of a small nucleolar RNA gene on mouse chromosome 12"Genomics. 79. 483-486 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kono, T., Sotomaru, Y., Katsuzawa, Y., L, Dandolo.: "Mouse parthenogenetic embryos with monoallelic H19 expression can develop today 17.5 of gestation"Dev. Biol.. 243. 294-300 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Obata, Y., Kono, T.: "Maternal primary imprinting is established at a specific time for each gene throughout oocyte growth"J. Biol. Chem.. 277. 5285-5289 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno, Y., Sotomaru, Y., Katsuzawa, Y., Kono, T., Okazaki, Y., et al.: "Asb4,Ata3,and dcn are novel imprinted genes identified by high-throughput screening using RIKEN cDNA microarry"BBRC. 290. 1499-1505 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ono, Y., et al.: "Production of cloned mice from embryonic stem cells arrested at metaphase"Reproduction. 122. 731-736 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hatada, I., Morita, S., Obata, Y., Sotomaru, Y., Shimoda, M., Kono, T.: "Identification of a New Imprinted Gene, Rian, on Mouse Chromosome 12 by Fluorescent Differential Display Screening"J. Biochem.. 130. 187-190 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sotomaru, Y., Kawase, Y., Obata, Y., Hatada, I., Kono, T.: "Disruption of lmprinted Expression of U2afbp-rs/U2af1-rs1 Gene in Mouse Parthenogenetic Fetuses"J. Biol.Chem.. 276. 26694-26698 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sotomaru, Y., Katsuzawa, Y., Domeki, I., Kono, T.: "Determination by Real-Time RT-PCR of Imprinted Expression of the Insulin-Like Growth Factor II(lgf2)Gene in Mouse Uniparental Fetuses"J. Reprod. Dev.. 47. 139-144 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ono, Y., Shimozawa, N., Ito, M., Kono, T.: "Cloned mice from fetal fibroblast cells arrested at metaphase by a serial nuclear transfer"Biol. Reprod.. 64. 44-50 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueda, T., Abe, K., Miura, A., Yuzuriha, M., et al.: "The paternal methylation imprint of the H19 locus is acquired in the gonocyte stage during fetal testis development"Genes to Cells. 5. 649-659 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tada, T., Obata, Y., Tada, M., Goto, Y., Nakatsuji, N., et al.: "Imprint switching for non-random X-chromosome inactivation during mouse oocyte growth"Development. 127. 3101-3105 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Obata, Y.Ono, Y., Akuzawa, H., Kwon, O.Y., Yoshizawa, M., Kono, T.: "Post-implantation developmental of mouse androgenetic embryos produced by in-vitro fertilization of enucleated oocytes"Hum. Reprod.. 15. 874-880 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Bao, S., Obata, Y., Carroll, J., Kono, T.: "Epigenetic modifications necessary for normal are established during oocyte growth in mice"Biol. Reprod.. 62. 616-621 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Bao S., et al.: "Development of bovine oocytes recon reconstructed with a nucleus from growing stage oocytes after fertilization in vitro"Theriogenology. 59. 1231-1239 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimozawa N., et al.: "Abnormalities in Cloned Mice Are Not Transmitted to the Progeny"Genesis. 34. 203-207 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] ObataY., et al.: "Maturation of mouse fetal germ cells in vitro"Nature. 418. 497-498 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimozawa, N., et al.: "Direct Production of Gene-targeted mice from ES cells by nuclear transfer and gene transmission to their Progeny"Exp. Anim.. 51. 375-381 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Bao, S.,et al.: "Nuclear competence for maturation and pronuclear formation in mouse oocytes"Hum Reprod. 17. 1311-1316 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sotomaru, Y., et al.: "Unregulated Expression of the Imprinted Genes H19 and Igf2r in Mouse Uniparental Fetuses"J. Biol. Chem.. 277. 12474-12478 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimoda, M.: "Imprinting of a Small Nucleolar RNA Gene on Mouse Chromosome 12"Genomics. 79. 483-486 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kono, T., et al.: "Mouse parthenogenetic embryos with monoallelic H19 expression can develop to day 17.5 of gestation"Dev. Biol.. 243. 294-300 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Obata, Y., Kono, T.: "Maternal primary imprinting is established at a cific time for each individual gene throughout oocyte growth"J. Biol. Chem.. 277. 5285-5289 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno Y., et al.: "Asb4, Ata3, and Dcn Are Novel Imprinted Genes Identified by High-Throughput Screening Using RIKEN cDNA Microarry"BBRC. 290. 1499-1505 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ono, Y., et al.: "Production of cloned mice from embryonic stem cells arrested at metaphase"Reproduction. 122. 731-736 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hatada, I., et al.: "Identification of a New Imprinted Gene, Rian, on Mouse Chromosome 12 by Fluorescent Differential Display Screening"J. Biochem.. 130. 187-190 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sotomaru, Y., et al.: "Disruption of Imprinted Expression of U2afbp-rs/U2af1-rs1 Gene in Mouse Parthenogenetic Fetuses"J. Biol. Chem.. 276. 26694-26698 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sotomaru, Y., et al.: "Determination by Real-Time RT-PCR of Imprinted Expression of the Insulin-Like Growth Factor II(lgf2)Gene in Mouse Uniparental Fetuses"J. Reprod. Dev.. 47. 139-144 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ono, Y., et al.: "Cloned mice from fetal fibroblast cells arrested at metaphase by a serial nuclear transfer"Biol. Reprod.. 64. 44-50 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueda, T., et al.: "The paternal methylation imprint of the H19 locus is acquired in the gonocyte stage during fetal testis development"Genes to Cells. 5. 649-659 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tada, T., et al.: "Imprint switching for non-random X-chromosome inactivation during mouse oocyte growth"Development. 127. 3101-3105 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Obata, Y., et al.: "Post-implantation developmental of mouse androgenetic embryos produced by in-vitro fertilization of enucleated oocytes"Hum Reprod.. 15. 874-880 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Bao, S., wt al.: "Epigenetic modifications necessary for normal development are established during oocyte growth in mice"Biol. Reprod.. 62. 616-621 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Bao, S., Ushijima, H., Hirose, A., Fumihito, A., Ono, Y., Kono, T.: "Development of bovine oocytes reconstructed with a nucleus from growing stage oocytes after fertilization in vitro"Theriogenology. 59. 1231-1239 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimozawa, N., Ono, Y., Kimoto, S., Hioki, K., Araki, Y., Shinkai, Y., Kono, T., Ito, M.: "Abnormalities in cloned mice are not transmitted to the progeny"Genesis. 34. 203-207 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Obata, Y., Kono, T.Hatada I.: "Maturation of mouse fetal germ cells in vitro"Nature. 418. 497-498 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimozawa, N, Ono, Y., Muguruma, K., Hioki, K., Arai, Y., Kono, T., Ito, M.: "Direct production of gene-targeted mice from ES cells by nuclear transfer and gene transmission to their progeny"Exp.Anim.. 51. 375-381 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Bao, S., Obata, Y., Ono, Y., Futatsumata, N., Niimura, S., Kono, T.: "Nuclear competence for maturation and pronuclear formation in mouse oocytes"Human Reprod.. 17. 1311-1316 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sotomaru, Y., Katsuzawa, Y., Hatada, I., Obata, Y., Sasaki, H., Kono, T.: "Unregulated expression of the imprinted genes H19 and Igf2r in mouse uniparental fetuses"J.Biol.Chem.. 277. 12474-12478 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Shimoda, M., Morita, S., Obata, Y., Sotomaru, Y., Kono, T., Hatada, I.: "Imprinting of a small nucleolar RNA gene on mouse chromosome 12"Genomics. 79. 483-486 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kono, T., Sotomaru, Y., Katsuzawa, Y., L, Dandolo: "Mouse parthenogenetic embryos with monoallelic H19 expression can develop to day 17.5 of gestation"Dev.Biol.. 243. 294-300 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Obata, Y., Kono, T.: "Maternal primary imprinting is established at a specific time for each gene throughout oocyte growth"J.Biol.Chem.. 277. 5285-5289 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizuno, Y., Sotomaru, Y., Katsuzawa, Y., Kono, T., Okazaki, Y., et al.: "Asb4,Ata3,and dcn are novel imprinted genes identified by high-throughput screening using RIKEN cDNA microarry"BBRC. 290. 1499-1505 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sotomaru Y., Katsuzawa Y., Hatada I., Obata Y., Sasaki H., Kono T.: "Undregulated Expression of the Imprinted Genes H19 and Igf2r in Mouse Uniparental Fetuses"J. Biol. Chem.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Obata Y., Kono T.: "Maternal primary imprinting is estabished at a cific time for each individual gene throughout oocyte growth"J. Biol. Chem.. 277. 5285-5289 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kono T., Sotomaru Y., L Dandolo.: "Mouse parthenogenetic embryos with mono-allelic H19 expression can develop to day 17.5 of gestation"Dev. Biol.. 243. 294-300 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ono Y., Shimozawa N., Muguruma K., Kimoto S., Hioki K., Tachibana M., Ito M., Kono T.: "Cloned mice from embryonic stem cells arrested at metaphase"Reproduction. 122. 731-736 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hatada I., Morita S., Obata Y., Sotomaru Y., Shimoda M., Kono T.: "Identification of a new imprinted gene, Rian, on mouse chromosome 12 by fluorescent differential display screening"J. Biochem.. 130. 187-190 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sotomaru Y., Kawase Y., Obata Y., Hatada I., Kono T.: "Disruption of imprinted expression of U2afbp-rs/U2af1-rs1 gene in mouse parthenogenetic fetuses"J. Biol. chem.. 276. 26694-26698 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sotomaru Y., Katsuzawa Y., Domeki I., Kono T.: "Determination by real-time RT-PCR of imprinted expression of the insulin-like growth factor II(Igf2) gene in mouse uniparental fetuses"J. Reprod. Dev.. 47. 139-144 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ono Y., Shimozawa N., Ito M., Kono T.: "Cloned mice from fetal fibroblast cells arrested at metaphase by a serial nuclear transfer"Biol. Reprod.. 64. 44-50 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 塩田邦郎, 松林秀彦, 河野友宏, 他86名: "妊娠の生物学"永井書店. 396 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 鈴木秋悦, 佐藤英明, 河野友宏, 他44名: "卵子研究法"養賢堂. 405 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Obata,Y.,Ono,Y.,Akuzawa,H.,Kwon,O.Y.,Yoshizawa,M.,Kono,T: "Post implantation developmental of mouse androgenetic embryos produced by in vitro fertilization of the enucleated oocytes"Human Reproduction. 15・4. 874-880 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tada,T.,Obata,Y.,Tada,M.,Goto,Y.,Nakatsuji,N.,Tan,S.S.,Kono,T.,Takagi,N.: "Imprint switching for non-random X-chromosome inactivation during mouse oocyte growth"Development. 127. 3101-3105 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ueda,T.,Abe,K.,Miura,A.,Yuzuriha,M.,Zubair,M.,Noguchi,M.,Niwa,K.,Kono,T.: "The paternal methylation inprint of the H19 locus is acquired in the gonocyte stage during fetal testis development"Genes to cells. 5. 649-659 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 尾畑やよい,包斯琴,河野友宏.: "卵母細胞の核移植"蛋白質核酸酸素. 45・13. 2030-2036 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kawase,Y.,Moriki,A.,Minato,Y.,Hamano,S.,Matsukawa,K.,Kono,T.: "Analysis of lgf2 and Lgf2r genes expression by RT-PCR in bovine fetuses"Jaurnal of Mammalian Qva Research. 17. 124-127 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ono,Y.,Shimozawa,N.,Ito,M.,Kono,T.: "Cloned mice from fetal fibroblast cells arrested at metaphase by a serial nuclear transfer"Biology of Reproduction. 64. 44-50 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kono, T.: "The influence of epigenetic changes during oocyte growth on nuclear reprogramming after nuclear transfer"Journal of Fertility and Development. 10. 593-598 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Bao, S. , Obata, Y. , Carrol, J. , Kono, T.: "Epigenetic modification necssary for normal development are established in during oocyte growth in mice"Biology of Reproduction. 62. 616-621 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Obata, Y. , Akuzawa, H. , Kwon, O. Y. , Yoshizawa, M. , Kono, T.: "Post implantation developmental of mouse androgenetic embryos produced by in vitro fertillization of the enucleated oocytes"Human Reproduction. 15(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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