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Validation of PSD-Zip70 knockout mice as a novel mouse model for neurodevelopmental disorder.

Research Project

Project/Area Number 15K21319
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurophysiology / General neuroscience
Basic / Social brain science
Research InstitutionIwate Medical University

Principal Investigator

Mayanagi Taira  岩手医科大学, 医学部, 講師 (20432544)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
KeywordsPSD-Zip70 / 前頭前皮質 / シナプス / 発達障害 / 行動解析 / ノックアウトマウス / 動物モデル / prefrontal cortex / 不安 / Rap2 / ストレス / 脳機能 / トランスジェニックマウス
Outline of Final Research Achievements

Postsynaptic protein PSD-Zip70 knockout (PSD-Zip70KO) mice possess defects in glutamate synapse transmission in the prefrontal cortex (PFC). To evaluate whether PSD-Zip70KO mice can be used as a modele for neurodevelopmental disorders such as autism spectrum disorder (ASD), we investigated their behavioral traits. As a result, PSD-Zip70KO mice did not exhibit stereotypical behavior or social ability defect, as typical ASD-like behavior. On the other hand, PSD-Zip70KO mice exhibited anxiety even without stress, and the trait was exacerbated by SD stress. Rap2 was activated and phosphorylation level of AMPA receptor GluA2 subunit at Ser880 was prominently elevated in SD-stressed mice, which leads internalization of surface-expressed AMPA receptors and decreases postsynaptic responsiveness. The PSD-Zip70-Rap2-related PFC hypofunction is involved in specifically social stress-induced anxiety. Our finding would provide valuable basis to analyze the mechanism for expression of anxiety.

Report

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

    (6 results)

All 2018 2017 2016 2015

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (2 results)

  • [Journal Article] Na+/H+ exchange regulatory factor 1 is required for ROMK1 K+ channel expression in the surface membrane of cultured M-1 cortical collecting duct cells.2017

    • Author(s)
      Takashi Suzuki, Kazuyoshi Nakamura, Taira Mayanagi, Kenji Sobue, Manabu Kubokawa.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 489 (2) Issue: 2 Pages: 116-122

    • DOI

      10.1016/j.bbrc.2017.05.104

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Myocardin-related transcription factor A (MRTF-A) activity-dependent cell adhesion is correlated to focal adhesion kinase (FAK) activity.2016

    • Author(s)
      Kishi Takayuki, Mayanagi Taira, Iwabuchi Sadahiro, Akasaka Toshihide, Sobue Kenji.
    • Journal Title

      Oncotarget

      Volume: 7 Issue: 44 Pages: 72113-72130

    • DOI

      10.18632/oncotarget.12350

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Docosahexaenoic Acid Promotes Axon Outgrowth by Translational Regulation of Tau and Collapsin Response Mediator Protein 2 Expression.2016

    • Author(s)
      Toshinari Mita* Taira Mayanagi*, Hiroshi Ichijo, Kentaro Fukumoto, Kotaro Otsuka, Akio Sakai, Kenji Sobue. (* equal contribution)
    • Journal Title

      Journal of Biological Chemistry

      Volume: 291 Issue: 10 Pages: 4955-4965

    • DOI

      10.1074/jbc.m115.693499

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] SD-Zip70-deficiency causes prefrontal hypofunction associated with glutamatergic synapse maturation defects by dysregulation of Rap2 activity.2015

    • Author(s)
      Taira Mayanagi, Hiroki Yasuda, and Kenji Sobue
    • Journal Title

      Journal of Neuroscience

      Volume: 35 Issue: 42 Pages: 14327-14340

    • DOI

      10.1523/jneurosci.2349-15.2015

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] ストレス起因性の不安におけるRap2活性化を伴う前頭前皮質の機能低下の関与2018

    • Author(s)
      真柳 平、祖父江 憲治
    • Organizer
      日本生化学会東北支部第84回例会 (矢巾)
    • Related Report
      2017 Annual Research Report
  • [Presentation] Involvement of Rap2-mediated prefrontal dysfunction in social stress-induced anxiety.2018

    • Author(s)
      Taira Mayanagi, Kenji Sobue
    • Organizer
      第41回日本神経科学大会 (神戸)
    • Related Report
      2017 Annual Research Report

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Published: 2015-04-16   Modified: 2025-11-18  

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