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遺伝子改変技術確立に基づき作製したOXTR遺伝子KOハタネズミによる共感性解析

Publicly Offered Research

Project AreaEmpathic system
Project/Area Number 16H01480
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionTohoku University

Principal Investigator

西森 克彦  東北大学, 農学研究科, 教授 (10164609)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥11,180,000 (Direct Cost: ¥8,600,000、Indirect Cost: ¥2,580,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Keywords共感性 / 平原ハタネズミ / Microtus ochrogaster / オキシトシン受容体 / 側坐核 / 向社会行動 / Consolation Behavior / オキシトシン / 共感性行動 / 向社会性行動 / 慰め行動 / バソプレッシン受容体V1aR / CRISPR/Cas9 / Prairie Vole
Outline of Annual Research Achievements

平原ハタネズミの生殖工学的な医術開発を背景に、CRISPR/Cas9法を利用して、世界で始めてOXTR遺伝子KOハタネズミ(平原ハタネズミ:OXTR(+/-))作製に成功した。得られたヘテロ型OXTR遺伝子KOハタネズミより雄ホモ型OXTR遺伝子KOハタネズミ(OXTR(-/-))を得て、ヒト不安・強迫性障害が同障害の動物モデルで反映されるとされるガラス玉覆い隠し試験を行った結果、OXTR遺伝子KOハタネズミは顕著な異常を見せた。薬剤誘導型(VPA処理)や遺伝子変異型(NL3R451C、Shank3(-/-)等)のASDモデルマウスで見いだされる社会記憶試験(Three chamber test)をOXTR(-/-)平原ハタネズミに初めて適用したところ、やはり明瞭な社会記憶障害が確認された。これらの結果についてはHorie, K., Iet al. (2018) Hormones and Behavior. (In press)に詳細を報告した。引き続き、Electrical foot shockを与えた雌に対するペア雄の共感性についても、明瞭な異常をOXTR KO平原ハタネズミ雄で確認出来た。共感性異常の解析については、別に作成したOXTR-IRES-Cre平原ハタネズミをマウスと比較解析し、前帯状皮質(anterior cingulate cortex)から側坐核(Nucleus accumbens)に投射する新たな特異的OXTR発現性ニューロンの存在を見いだした。
本研究の推進により、高度な向社会行動にの神経基盤解析に平原ハタネズミが適切である証左を得た。向社会性が損なわれるASD(自閉症スペクトラム障害)での障害神経回路解析や、抗ASD性の治療薬候補などの薬理解析に最適と予想される遺伝子変換平原ハタネズミの実験例を示すことに成功した。

Research Progress Status

平成29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

平成29年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (24 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 9 results,  Open Access: 4 results) Presentation (12 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Remarks (1 results)

  • [Int'l Joint Research] Emory University/Northwestern University/Louisiana State University(米国)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] Emory University(米国)

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Melanin concentrating hormone modulates oxytocin-mediated marble burying.2018

    • Author(s)
      Nayna, M., Sanathara, N.M., Garau, C., Alachkar, A., Wang, L., Wang, Z., Nishimori, K., Xu, X. and Civelli, O.
    • Journal Title

      J.Neuropharmacology

      Volume: 128 Pages: 22-32

    • DOI

      10.1016/j.neuropharm.2017.09.008

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Oxytocin Signaling in the Lateral Septum Prevents Social Fear during Lactation.2018

    • Author(s)
      Menon, R., Grund, T., Zoicas, I., Althammer, F., Fiedler, D., Biermeier, V., Bosch, O. J., Hiraoka, Y.,  Nishimori, K., Eliava, M., Grinevich, V., & Neumann I. D.
    • Journal Title

      Current Biology

      Volume: 28 Issue: 7 Pages: 1066-1078.e6

    • DOI

      10.1016/j.cub.2018.02.044

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The anorexigenic neural pathways of oxytocin and clinical implication2018

    • Author(s)
      Maejima Y, Yokota S, Nishimori K, Shimomura K
    • Journal Title

      Neuroendocrinology

      Volume: 印刷中 Issue: 1 Pages: 91-104

    • DOI

      10.1159/000489263

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oxytocin receptor is regulated by Peg32018

    • Author(s)
      Frey Wesley D.、Sharma Kaustubh、Cain Terri L.、Nishimori Katsuhiko、Teruyama Ryoichi、Kim Joomyeong
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 8 Pages: 1-12

    • DOI

      10.1371/journal.pone.0202476

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxytocin receptor signaling contributes to olfactory avoidance behavior induced by an unpleasant odorant2018

    • Author(s)
      Osada K, Ohta T, Takai R, Miyazono S, Kashiwayanagi M, Hidema S, Nishimori K
    • Journal Title

      Biology Open

      Volume: 7 Pages: 9-9

    • DOI

      10.1242/bio.029140

    • NAID

      120006541973

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxytocin receptor knockout prairie voles generated by CRISPR/Cas9 editing show reduced preference for social novelty and exaggerated repetitive behaviors.2018

    • Author(s)
      Horie K, Inoue K, Suzuki S, Adachi S, Yada S, Hirayama T, Hidema S, Young LJ, Nishimori K.
    • Journal Title

      Horm Behav.

      Volume: 18 Pages: 1-10

    • DOI

      10.1016/j.yhbeh.2018.10.011

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxytocin stimulates hippocampal neurogenesis via oxytocin receptor expressed in CA3 pyramidal neurons2017

    • Author(s)
      in, Y.-T., Chen, C.-C., Huang, C.-C., Nishimori, K., & Hsu, K.-S.
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1-16

    • DOI

      10.1038/s41467-017-00675-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Chick derived induced pluripotent stem cells by the poly-cistronic transposon with enhanced transcriptional activity.2017

    • Author(s)
      Katayama M, Hirayama T, Tani T, Nishimori K, Onuma M, Fukuda T.
    • Journal Title

      J Cell Physiol

      Volume: 印刷中 Issue: 2 Pages: 990-1004

    • DOI

      10.1002/jcp.25947

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Oxytocin-Oxytocin Receptor Systems Facilitate Social Defeat Posture in Male Mice2017

    • Author(s)
      Nasanbuyan Naranbat、Yoshida Masahide、Takayanagi Yuki、Inutsuka Ayumu、Nishimori Katsuhiko、Yamanaka Akihiro、Onaka Tatsushi
    • Journal Title

      Endocrinology

      Volume: 159 Issue: 2 Pages: 763-775

    • DOI

      10.1210/en.2017-00606

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] アルコール摂取による有害効果への内在性Oxytocin系の抑制作用について2019

    • Author(s)
      大塚彩乃、日出間 志寿、西森克彦
    • Organizer
      2019年日本農芸化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 高脂肪食摂取マウスにおける社会記憶の低下と末梢オキシトシン投与による社会記憶改善効果2019

    • Author(s)
      林遼太郎,日出間志寿,福光聡,仲川清隆、西森克彦
    • Organizer
      2019年日本農芸化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Activation of Oxtr+ neurons in LS improve abnormal social behaviors.2018

    • Author(s)
      堀合眞知、木野崎萌、矢田紗織、日出間志寿、西森克彦
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Analysis of empathic neural circuit regulated by oxytocin.2018

    • Author(s)
      矢田紗織、堀江謙吾、日出間志寿、西森克彦
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The male Oxtr KO prairie voles showed higher obsessive behavior and decreased paternal behavior2018

    • Author(s)
      堀江 謙吾  安達 紗希 矢田 紗織  日出間 志寿  西森 克彦
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 大会実行委員会主催シンポジウム 「脊椎・無脊椎動物のストレス応答機構の多様性と普遍性」西森克彦(東北大院・農) 「オキシトシン・受容体系による動物社会行動の脳内制御機構、その破綻と自閉症スぺクトラム障害」2018

    • Author(s)
      西森克彦
    • Organizer
      第43回日本比較内分泌学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 内側視索前野のオキシトシン受容体発現ニューロンは乳汁射出を制御する2018

    • Author(s)
      日出間 志寿、矢田沙織、堀江謙吾、林遼太郎、水上浩明、西森克彦
    • Organizer
      第43回日本比較内分泌学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Analysis of empathic neural circuits regulated by oxytocin.2018

    • Author(s)
      S. YADA, K. HORIE, S. HIDEMA, K.NISHIMORI
    • Organizer
      北米神経科学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Oxytocin receptor-positive dentate neurons mediate the effects of state-dependent memory on social behavior.2018

    • Author(s)
      M. MEYER, K. NISHIMORI, J.RADULOVIC.
    • Organizer
      北米神経科学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Distribution of vasopressin receptor 1a and 1b in mouse brain.2018

    • Author(s)
      Horie K, Yada S, Inoue K., Larry J Young, Nishimori K.
    • Organizer
      北米神経科学会
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 自閉症スペクトラム障害治療薬の開発に向けたオキシトシン受容体アゴニスト探索2016

    • Author(s)
      鈴木紳吾、堀江謙吾、岸貴之、井上飛鳥、矢田紗織、日出間志寿、青木淳賢、西森克彦
    • Organizer
      第39回日本分子生物学会年会
    • 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
      2016 Annual Research Report
  • [Presentation] 1/ Generation of oxytocin receptor modified prairie voles by using CRISPR/Cas.2016

    • Author(s)
      K. HORIE, T. HIRAYAMA, S. SUZUKI, T. FUKUDA, S. HIDEMA, K. NISHIMORI
    • Organizer
      Neuroscience 2016 Annual Meeting
    • Place of Presentation
      San Diego/USA
    • Year and Date
      2016-11-12
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 東北大学大学院農学研究科・応用生命科学専攻

    • URL

      http://www.biochem.tohoku.ac.jp//bunsi/index-j.html

    • Related Report
      2016 Annual Research Report

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Published: 2016-04-26   Modified: 2022-01-28  

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