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A genetic analysis of REM sleep based on a novel sleep related gene Nalcn

Research Project

Project/Area Number 15K18966
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionUniversity of Tsukuba

Principal Investigator

FUJIYAMA Tomoyuki  筑波大学, 国際統合睡眠医科学研究機構, 特別研究員(PD) (00635089)

Co-Investigator(Renkei-kenkyūsha) KANDA Takeshi  筑波大学, 国際統合睡眠医科学研究機構(WPI-IIIS), 助教 (00599821)
MIYOSHI Chika  筑波大学, 国際統合睡眠医科学研究機構(WPI-IIIS), 助教 (60613437)
FUNATO Hiromasa  筑波大学, 国際統合睡眠医科学研究機構(WPI-IIIS), 客員教授 (90363118)
YANAGISAWA Masashi  筑波大学, 国際統合睡眠医科学研究機構(WPI-IIIS), 教授/機構長 (20202369)
Research Collaborator MIZUNO Seiya  筑波大学, 生命科学動物資源センター(LARC), 助教 (10633141)
TAKAHASHI Satoru  筑波大学, 生命科学動物資源センター(LARC), 教授 (50271896)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsレム睡眠 / Forward genetics / CRISPR / ENU mutagenesis / Dreamless / Nalcn / REM sleep / Sleep / Sik3 / Sleepy / 一塩基置換 / in situ hybridization
Outline of Final Research Achievements

Dreamless mice, which was established from an ENU mutagenized mouse, showed a decreased rapid-eye-movement (REM) sleep. Subsequent genome sequencing including whole exome sequencing and genetic linkage analysis revealed that the mutation in Dreamless mice affects a gene Nalcn, which codes for an ion-channel protein and has previously been implicated in the circadian control of the neuronal excitability. In addition, Funato and Fujiyama et al. demonstrated that the reproduction of the same mutation in Dreamless mice via CRISPR/Cas9 system could recapiturate thier phenotypes, which defined the causality of Dreamless mice. Electrophysiologically assessed brain waves were altered in Dreamless mutant mice compared with controls, during REM and NREM sleep, and during wakefulness. These findings implied that a novel sleep related gene Nalcn is involved in the regulation of all vigilance states, but especially in REM sleep.

Report

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

    (9 results)

All 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (4 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] UT Southwestern Medical Center(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Identification of mutations through dominant screening for obesity using C57BL/6 substrains2016

    • Author(s)
      Hossain MS., Funato H, and Yanagisawa M et al.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 32453-32453

    • DOI

      10.1038/srep32453

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Forward-genetics analysis of sleep in randomly mutagenized mice2016

    • Author(s)
      Funato H and Yanagisawa M et al.
    • Journal Title

      Nature

      Volume: 539(7629) Issue: 46 Pages: 378-383

    • DOI

      10.1038/nature20142

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO22015

    • Author(s)
      Ruffault PL, D'Autreaux F, Hayes JA, Nomaksteinsky M, Autran S, Fujiyama T, Hoshino M, Hagglund M, Kiehn O, Brunet JF, Fortin G, Goridis C.
    • Journal Title

      Elife

      Volume: Apr 13;4

    • DOI

      10.7554/elife.07051

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 連鎖解析と全エクソームシーケンスによるDreamless変異家系特異的な一塩基置換の同定とCRISPR/Casによる再現2016

    • Author(s)
      藤山 知之、三好 千香、佐藤 牧人、水野 聖哉、柳沢 正史、船戸 弘正
    • Organizer
      第121回日本解剖学会
    • Place of Presentation
      ビッグパレットふくしま(福島県郡山市)
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] Identification of a single nucleotide substitution specific to the 
Dreamless mutant mouse by linkage analysis and whole exome sequencing, and its genetic verification by CRISPR2016

    • Author(s)
      藤山知之 三好千香 佐藤牧人 上田壮志 水野聖哉 高橋智 村本玄紀 浅野冬樹 本多隆利 岩崎加奈子 一久綾 柿崎美代 堀田範子 管野里美 石川有紀子 三浦郁生 鈴木智広 若菜茂晴 ビベククマル ジョセフタカハシ 船戸弘正 柳沢正史
    • Organizer
      The 4th Annual IIIS Symposium
    • Place of Presentation
      筑波大学(茨城県つくば市)
    • Year and Date
      2016-02-26
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of a single nucleotide substitution specific to the Dreamless mutant mouse pedigree by linkage analysis and whole exome sequencing, and its genetic verification by CRISPR2015

    • Author(s)
      藤山知之 三好千香 佐藤牧人 上田壮志 水野聖哉 高橋智 村本玄紀 浅野冬樹 本多隆利 岩崎加奈子 一久綾 柿崎美代 堀田範子 管野里美 石川有紀子 三浦郁生 鈴木智広 若菜茂晴 ビベククマル ジョセフタカハシ 船戸弘正 柳沢正史
    • Organizer
      Neuroscience 2015, SfN’s 45th Annual Meeting
    • Place of Presentation
      シカゴ(米国)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 連鎖解析と全エクソームシーケンスによるDreamless変異家系特異的な一塩基置換の同定とCRISPR法による再現2015

    • Author(s)
      藤山知之 船戸弘正 三好千香 佐藤牧人 水野聖哉 上田壮志 高橋智 村本玄紀 Liu Qinghua 一久綾 堀田範子 柿崎美代 管野里美 石川有紀子 浅野冬樹 本多隆利 三浦郁生 鈴木智広 若菜茂晴 柳沢正史
    • Organizer
      第38回日本神経科学大会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
  • [Remarks] Genetic Analysis Identifies Proteins for Sleep

    • URL

      http://www.tsukuba.ac.jp/en/research-list/p201611041539

    • Related Report
      2016 Annual Research Report

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Published: 2015-04-16   Modified: 2022-02-16  

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