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ANALYSIS OF CYCLIC CHANGES OF X CHROMOSOME ACTIVITY IN MOUSE DEVELOPMENT

Research Project

Project/Area Number 13440223
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 遺伝
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

TAKAGI Nobuo  Hokkaido Univ., Grad. Sch. Environ. Earth Sci., Prof., 大学院・地球環境科学研究科, 教授 (20001852)

Co-Investigator(Kenkyū-buntansha) 後藤 友二  北海道大学, 大学院・地球環境科学研究科, 日本学術振興会特別研究員(PD)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥10,700,000 (Direct Cost: ¥10,700,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥7,700,000 (Direct Cost: ¥7,700,000)
KeywordsMouse / Early development / X-inactivation / Dosage compensation / Xist gene / FISH / GFP / ES cells / X染色体 / 不活性化 / Xist
Research Abstract

Only the morphologically normal X chromosome is inactivated in female mice heterozygous for Searle's X-autosome translocation. We performed a visual study of the primary and secondary events that culminate in the cmpletely non-random inactivation in female embryos having his translocation. The data we have obtained so far indicate that the initial choice of the future inactive X chromosome is biased: the degree of skewing is somewhere between 70 : 30% and 90 : 10% in favor of the morphologically normal X chromosome. The majority of genetically unbalanced cells that inactivate a translocated X chromosome are quickly eliminated from the embryo by proper E8.5.
Applying RNA fluorescence in situ hybridization to parthenogenetic embryos with two maternally derived X (Xm) chromosomes and embryos with X chromosome aneuploidy such as Xp0 (Xp, paternally derived X chromosome), XmXmXp and XmXmY, we studied the control of Xist. Tsix expression for silencing the X chromosome in mice. The data show t … More hat the paternally derived Xist allele is highly expressed in every cell of the embryo from the 4-cell stage onward, irrespective of the number of X chromosomes in a diploid cell. The high level of Xist transcription is maintained in non-epiblast cells culminating in Xp-inactivation, whereas in Xp0 embryos it is terminated by the blastocyst stage, probably as a result of counting the number of X chromosomes in a cell occurring at the morula/blastocyst stage. Xist is also down-regulated in epiblast cells of XmXp and XmXmXp embroys to make X-inactivation random.
Three female ES cell lines carrying X-linked GFP and lacZ transgenes in cis were established for visual study of X-inactivation in vitro. X-inactivation assessed by extinction of GFP fluorescence and expression of β-galactosidase appeared normal in differentiating embryoid bodies. However, loss of GFP fluorescence does not coincide with the lack of β-galactosidase activity in a considerable proportion of apparently differentiated cells in response to retinoic acid treatment. It is likely that X-inactivation does not occur normally in such cells. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

Research Products

(20 results)

All Other

All Publications

  • [Publications] Matsui, J.: "control of Xist expression for imprinted and random X chromosome inactivation in mice"Human Molecular Genetics. 10・13. 1393-1401 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takagi, N.: "The role of X-chromosome inactivation in the manifestation of Rett syndrome"Brain and Development. 23Supplement. S182-S185 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 高木 信夫: "X染色体の不活性化"生化学. 74・5. 377-390 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno, H.: "Developmental abnormalities in mouse embryos tetrasomic for chromosome 11:Apparent similarity to embryos functionally disomic for the X chromosome"Genes and Genetic Systems. 77・4. 269-276 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goto, Y.: "Developmental potential of mouse tetraploid cells in diploid【double arrow】tetraploid chimeric embryos"International Journal of Developmental Biology. 46・5. 741-745 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takagi N.: "Non-randam X chromosome inactivation in mouse embryos carrying Searle's T(X;16)16H translocation visualized by the X-linked lacZ and GFP transgenes"Cytogenetic and Genome Research. 99・1-4(In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsui J., Goto Y., Takagi N.: "Control of Xist expression for imprinted and random X chromosome inactivation in mice"Human Molecular Genetics. 10(13). 1393-1401 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takagi N.: "The role of X-chromosome inactivation in the manifestation of Rett syndrome"Brain and Development. 23(supplement). S182-S185 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuho H., Okamoto I., Takagi N.: "Developmental abnormalities in mouse embryos tetrasomic for chromosome 11 : Apparent similarity to embryos functionally disomic for the X chromosome"Genes and Genetic systems. 77(4). 269-2756 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Goto y., Matsui J., Takagi N.: "Developmental potential of mouse tetraploid cells in diploid【double arrow】tetraploid chimeric embryos"International Journal of Developmental Biology. 46(5). 741-745 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takagi N., Sugimoto M., Yamaguchi S., Ito M., Tan S.S., Okabe M.: "Non-random X chromosome inactivation in mouse embryos carrying Searle's T(X ; 16)16H translocation visualized by the X-linked lacZ and GFP transgenes"Cytogenetic and Genome Research. 99(1-4). in press

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsui, J., Goto, Y., Takagi, N.: "Control of Xist expression for imprinted and random X chromosome inactivation in mice"Human Molecular Genetics. 10・13. 1393-1401 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takagi, N.: "The role of X-chromosome inactivation in the manifestation of Rett syndrome"Brain and Development. 23 Supplement. S182-S185 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高木 信夫: "X染色体の不活性化"生化学. 74・5. 377-390 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizuno, H., Okamoto, I., Takagi, N.: "Developmental abnormalities in mouse embryos tetrasomic for chromosome 11 : Apparent similarity to embryos functionally disomic for the X chromosome"Genes and Genetic Systems. 77・4. 269-276 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Goto, Y., Matsui, J., Takagi, N.: "Developmental potential of mouse tetraploid cells in diploid【double arrow】tetraploid chimeric embryos"International Journal of Developmental Biology. 46・5. 741-745 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takagi N, Sugimoto M, Yamaguchi, S, Ito M, Tan SS, Okabe M: "Non-random X chromosome inactivation in mouse embryos carrying Searle's T(X ; 16)16H trnaslocation visualized by the X-linked lacZ and GFP transgenes"Cytogenetic and Genome Research. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsui, J., Goto, Y., Takagi, N.: "Control of Xist expression for imprinted and randomX chromosome inactivation in mice"Human Molecular Genetics. 10・13. 1393-1401 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takagi, N.: "The role of X-chromosome inactivation in the manifestation of Rett syndrome"Brain and Development. 23 Supplement. S182-S185 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 高木 信夫: "X染色体の不活性化"生化学. (印刷中).

    • Related Report
      2001 Annual Research Report

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Published: 2001-03-31   Modified: 2016-04-21  

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