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Development of therapy for myotonic dystrophy by analyzing splicing mechanism using new splicing quantitative system

Research Project

Project/Area Number 15H06161
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionThe University of Tokyo

Principal Investigator

YOSHIDA NATSUMI  東京大学, 生命科学ネットワーク, 特任助教 (10760069)

Project Period (FY) 2015-08-28 – 2017-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsmyotonic dystrophy (DM) / chloride channel (CLCN1) / MBNL / CELF / antisenseoligonucleotide / Tat peptide / CLCN1 / 筋強直性ジストロフィー / AON / TAT / 遺伝子 / 核酸 / 発現制御 / 病理 / 薬学 / 選択的スプライシング / クロライドチャネル
Outline of Final Research Achievements

Muscle hyper-excitability (myotonia) in patients with myotonic dystrophy is caused by the abnormality in alternative splicing of chloride channel (CLCN1). It is important for the treatment to normalize CLCN1 splicing. However, it was found that the genomic structures of mouse and human CLCN1 are considerably different, and we newly detected the abnormal splicing isoform exists in human CLCN1. So, it was necessary to quantify CLCN1 splicing by a new method using human CLCN1 genome. Therefore, we constructed a system to quantify only normal splicing, identify the sequence of antisense oligonucleotide that efficiently normalizes splicing of human CLCN1, and identify the splicing factor for the normalization. We expect that these results will be contributed to development of the treatment.

Report

(3 results)
  • 2017 Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (6 results)

All 2018 2017 2016 2015

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (4 results)

  • [Journal Article] Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy2018

    • Author(s)
      Ishiura Hiroyuki、Doi Koichiro、Mitsui Jun、Yoshimura Jun、Matsukawa Miho Kawabe、Takahashi Yuji、Date Hidetoshi、Matsukawa Takashi、Shimizu Jun、Koh Kishin、Takiyama Yoshihisa、Goto Jun、Morishita Shinichi、Tsuji Shoji
    • Journal Title

      Nature Genetics

      Volume: 50 Issue: 4 Pages: 581-590

    • DOI

      10.1038/s41588-018-0067-2

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Splicing of human chloride channel 12015

    • Author(s)
      Nakamura, T., Ohsawa-Yoshida, N., Zhao, Y., Koebis, M., Oana, K., Mitsuhashi, H., Ishiura, S.
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 5 Pages: 63-69

    • DOI

      10.1016/j.bbrep.2015.11.006

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] マウス膵ベータ細胞株MIN6の飢餓ストレスに対するlncRNAを介した遺伝子発現制御機構の探索2017

    • Author(s)
      土屋一郎、荒木海人、石井智子、吉田(大澤)奈摘、太田邦史
    • Organizer
      ConBio2017
    • Related Report
      2016 Annual Research Report
  • [Presentation] 土屋一郎、石井智子、吉田(大澤)奈摘、太田那史2016

    • Author(s)
      マウス膵β細胞株MIN6における飢餓ストレスに対すlncRNAを介した遺伝子発現制御の探索
    • Organizer
      The 39th Annual Meeting of the Molecular Biology Society of Japan
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] Identification of interactions between repeat RNAs and RNA binding proteins by the Yeast Three Hybrid system.2016

    • Author(s)
      Natsumi Ohsawa-Yoshida, Josephine GALIPON, Shoichi Ishiura, Kunihiro Ohta.
    • Organizer
      The 39th Annual Meeting of the Molecular Biology Society of Japan
    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
  • [Presentation] The optimization of antisense oligonucleotide therapy for the abnormality of CLCN1 alternative splicing in DM.2015

    • Author(s)
      Natsumi Ohsawa-Yoshida, Takumi Nakamura, Michinori Koebis, Shoichi Ishiura.
    • Organizer
      BMB2015
    • Place of Presentation
      神戸国際会議場(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report

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Published: 2015-08-26   Modified: 2019-03-29  

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