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Meiotic regulation and its epigenetic analyses of male-female differences using model mice carrying a balanced reciprocal translocation

Research Project

Project/Area Number 15K08334
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human genetics
Research InstitutionFujita Health University

Principal Investigator

Tsutsumi Makiko  藤田医科大学, 総合医科学研究所, 助教 (30377907)

Project Period (FY) 2015-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords均衡型染色体相互転座 / 減数分裂 / 不妊 / 習慣流産 / 精子形成 / 染色体転座
Outline of Final Research Achievements

Male carriers of balanced reciprocal translocation are often sterile due to azoospermia or oligozoospermia. While female carriers undergo recurrent miscarriages. The sexual dimorphism in the gametogenesis process is considered as a main contributing factor of these sex differences. However, it has not been fully elucidated yet. In this study, the meiotic processes were analyzed using a reciprocal translocation mouse model. Male model mice had apoptotic cells at the pachytene and the metaphase stages. Spermatocyte spreads showed that the derivative chromosomes were defective in synapsis and often co-localized with the XY body. Immunofluorescence analysis indicated meiotic sex chromosome inactivation (MSCI) failure in these cells, leading to spermatogenic arrest. These results suggest MSCI failure is a cause of sterility of male carriers.

Academic Significance and Societal Importance of the Research Achievements

均衡型相互転座の保因者は650人に1人という比較的高頻度で見られる。本研究では遺伝的バックグラウンドの異なる2種類の転座モデルマウスを解析することにより、それぞれの減数分裂時のクロマチン動態やエピジェネティック修飾を明らかにすると共に、妊孕性との関係を理解する手がかりを得た。このことは生殖問題に直面する転座保因者のより正確なリスク算定を将来行うのに役立つと期待される。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (4 results)

All 2017 2016 2015

All Presentation (4 results) (of which Int'l Joint Research: 2 results)

  • [Presentation] 均衡型相互転座モデルマウスの精子形成における性染色体不活化異常の発生機構2017

    • Author(s)
      堤真紀子、 加藤武馬、稲垣秀人、倉橋浩樹
    • Organizer
      ConBio2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Spermatogenic failure by impaired meiotic sex chromosome inactivation in a mouse with reciprocal translocation2016

    • Author(s)
      Makiko Tsutsumi, Takema Kato, Hidehito Inagaki, Tamae Ohye, Hiroki Kurahashi
    • Organizer
      ICHG2016
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2016-04-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Spermatogenic failure by impaired meiotic sex chromosome inactivation in a mouse with reciprocal translocation2016

    • Author(s)
      Makiko Tsutsumi, Takema Kato, Hidehito Inagaki, Tamae Ohye, Hiroki Kurahashi
    • Organizer
      ICHG 2016
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2016-04-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 均衡型相互転座保因者モデルマウスにおける減数分裂期の性染色体不活化異常の発生機構の解明2015

    • Author(s)
      堤真紀子, 加藤武馬, 稲垣秀人, 大江瑞恵, 倉橋浩樹
    • Organizer
      日本人類遺伝学会第60回大会
    • Place of Presentation
      京王プラザホテル(新宿)
    • Year and Date
      2015-10-14
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2020-03-30  

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