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A novel approach for identification of the genes responsible for hypertensive phenotype in SHRSP

Research Project

Project/Area Number 24790846
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Kidney internal medicine
Research InstitutionShimane University

Principal Investigator

OHARA Hiroki  島根大学, 医学部, 助教 (10609225)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords高血圧 / 疾患モデル / ストレス / コンジェニックラット / 交感神経
Research Abstract

Exaggerated sympathetic response to stress in the stroke-prone spontaneously hypertensive rat (SHRSP) have been implicated in the pathogenesis observed in this strain. Previously, by using a congenic strain constructed between SHRSP and the normotensive Wistar-Kyoto rat (WKY), we showed that a 1.8-Mbp region on chromosome 1 of SHRSP affects the sympathetic response to stress. In this study, subcongenic analyses further narrowed down the candidate region to a 1.2-Mbp fragment. Gene expression analysis and whole genome sequence analysis identified Stim1 as a strong candidate gene as a nonsense mutation was found in this gene of SHRSP. A western blot analysis confirmed a truncated form of STIM1 in SHRSP. In addition, the analysis revealed that the protein level of STIM1 in the brainstem of SHRSP was significantly lower when compared with WKY. Our results suggested that Stim1 is a strong candidate gene responsible for the exaggerated sympathetic response to stress in SHRSP.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (14 results)

All 2014 2013 2012 Other

All Journal Article (3 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (10 results) (of which Invited: 2 results) Remarks (1 results)

  • [Journal Article] Identification of Stim1 as a candidate gene for exaggerated sympathetic response to stress in the stroke-prone spontaneously hypertensive rat2014

    • Author(s)
      Ferdaus MZ, Xiao B, Ohara H, Nemoto K, Harada Y, Saar K, Hubner N, Isomura M, Nabika T
    • Journal Title

      PLoS ONE

      Volume: 9(4)

    • Related Report
      2013 Final Research Report
  • [Journal Article] Identification of Stim1 as a candidate gene for exaggerated sympathetic response to stress in the stroke-prone spontaneously hypertensive rat.2014

    • Author(s)
      Mohammed Zubaerul Ferdaus, Bing Xiao, Hiroki Ohara, Kiyomitsu Nemoto, Yuji Harada, Kathrin Saar, Norbert Hubner, Minoru Isomura, Toru Nabika
    • Journal Title

      PLOS ONE

      Volume: 9 Issue: 4 Pages: e95091-e95091

    • DOI

      10.1371/journal.pone.0095091

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The stroke-prone spontaneously hypertensive rat: Still a useful model for post-GWAS genetic studies?2012

    • Author(s)
      Nabika T
    • Journal Title

      Hypertens Res

      Volume: 35 Issue: 5 Pages: 477

    • DOI

      10.1038/hr.2012.30

    • NAID

      10030645486

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] ストレス性高血圧原因遺伝子としてのStim1の同定 : 高血圧モデルラットSHRSPを用いた研究2014

    • Author(s)
      大原浩貴,磯村実,並河徹
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島市
    • Related Report
      2013 Final Research Report
    • Invited
  • [Presentation] ストレス性高血圧原因遺伝子としてのStim1の同定:高血圧モデルラットSHRSPを用いた研究2014

    • Author(s)
      大原 浩貴、磯村 実、並河 徹
    • Organizer
      第91回日本生理学会大会
    • Place of Presentation
      鹿児島大学・鹿児島
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 遺伝的高血圧モデルラットSHRSPにおけるストレス性高血圧原因遺伝子の探索.2013

    • Author(s)
      大原浩貴,並河徹
    • Organizer
      第36回日本高血圧学会総会
    • Place of Presentation
      大阪市
    • Related Report
      2013 Final Research Report
  • [Presentation] ラット第1染色体に潜むストレス感受性と高血圧をつなぐ遺伝子の探索 : ストレス性高血圧の原因遺伝子同定を目指して2013

    • Author(s)
      大原浩貴、磯村実、並河徹
    • Organizer
      第49回高血圧関連疾患モデル学会学術総会
    • Place of Presentation
      東京都
    • Related Report
      2013 Final Research Report
  • [Presentation] ラット第1染色体に潜むストレス感受性と高血圧をつなぐ遺伝子の探索:ストレス性高血圧の原因遺伝子同定を目指して2013

    • Author(s)
      大原 浩貴、磯村 実、並河 徹
    • Organizer
      第49回高血圧関連疾患モデル学会学術総会
    • Place of Presentation
      日本大学・東京
    • Related Report
      2013 Annual Research Report
  • [Presentation] 遺伝的高血圧モデルラットSHRSPにおけるストレス性高血圧原因遺伝子の探索2013

    • Author(s)
      大原 浩貴、並河 徹
    • Organizer
      第36回日本高血圧学会総会
    • Place of Presentation
      大阪国際会議場・大阪
    • Related Report
      2013 Annual Research Report
  • [Presentation] Search for the genes responsible for exaggerated sympathetic response to stress in stroke-prone spontaneously hypertensive rat : genetic and molecular biological approach using congenic strains.2012

    • Author(s)
      Ohara H, Ferdaus MZ, Isomura M, Nabika T
    • Organizer
      15th International SHR Symposium/48th Japanese SHR Meeting
    • Place of Presentation
      Melbourne, Australia
    • Related Report
      2013 Final Research Report
  • [Presentation] ストレス感受性から見たSHRSPにおける高血圧原因遺伝子の探索2012

    • Author(s)
      大原浩貴,並河徹
    • Organizer
      第35回日本高血圧学会総会
    • Place of Presentation
      名古屋市
    • Related Report
      2013 Final Research Report
  • [Presentation] ストレス感受性から見たSHRSPにおける高血圧原因遺伝子の探索2012

    • Author(s)
      大原浩貴、並河徹
    • Organizer
      第35回日本高血圧学会総会
    • Place of Presentation
      ウェスティンナゴヤキャッスル(名古屋市)
    • Related Report
      2012 Research-status Report
  • [Presentation] Search for the genes responsible for exaggerated sympathetic response to stress in stroke-prone spontaneously hypertensive rat: genetic and molecular biological approach using congenic strains2012

    • Author(s)
      Hiroki Ohara, Mohammed Zubaerul Ferdaus, Minoru Isomura, Toru Nabika
    • Organizer
      第15回国際SHRシンポジウム&第48回高血圧関連疾患モデル学会
    • Place of Presentation
      メルボルン大学(メルボルン、オーストラリア)
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.med.shimane-u.ac.jp/pathology/

    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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