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Epilepsy in Girdin/ccdc88a knockout mice

Research Project

Project/Area Number 19K06464
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionInstitute for Developmental Research Aichi Developmental Disability Center

Principal Investigator

Iida Machiko  愛知県医療療育総合センター発達障害研究所, 障害モデル研究部, 主任研究員 (60465515)

Co-Investigator(Kenkyū-buntansha) 浅井 真人  愛知県医療療育総合センター発達障害研究所, 障害モデル研究部, 部長 (70543536)
田中 基樹  愛知県医療療育総合センター発達障害研究所, 障害モデル研究部, 研究員 (90584673)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsてんかん / Girdin/ccdc88a / モデル動物
Outline of Research at the Start

てんかんは、世界で最も多い慢性脳疾患の1つである。内側側頭葉てんかんは成人てんかんの中で最も多く、意識喪失を伴う自動症を特徴とし一部は強直間代発作(突然意識を喪失し、手足をつっぱるような全身の硬直の後、全身のけいれんを発症)に移行する。てんかん患者の意識喪失による、転倒・転落、溺水、運転事故などは社会的にもよく知られる深刻な問題である。薬物療法や外科的治療が有効ではあるが未だ約3割が難治である。本研究では、申請者らが見出した新規てんかん原因遺伝子欠損マウスを用いて、病理解析、電気生理学的解析、脳波解析等より、これまでにない新たなてんかん原理の解明と治療法の開発を目指す。

Outline of Final Research Achievements

In this study, we found two animal models of intractable epilepsy that mimic early-onset developmental epileptic encephalopathy (DEE) and adult-onset mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE with HS) by knocking out Girdin/ccdc88a gene in different cellular lineages. Furthermore, we found that depletion of Girdin causes impaired migration of progenitor cells of hippocampal interneurons, which is responsible for the pathogenesis of intractable epilepsy.

Academic Significance and Societal Importance of the Research Achievements

てんかんは世界で最も多い慢性脳疾患の1つである。薬物療法や外科的治療が有効とされるが、未だ約3割が難治となるため、新たな視点に立ったてんかん病態解明が求められる。そのためには、ヒト難治てんかんに類似した病態を示すモデル動物が必須である。本研究では、新規てんかん遺伝子Girdinを異なる条件で欠損させた2種類のマウスに、幼少期の難治てんかんである発達性てんかん性脳症、成人の難治てんかんである海馬硬化を伴う内側側頭葉てんかんに類似した病態を見出すことに成功した。さらに、このマウスに生じるてんかん症状が既存のヒト抗てんかん薬で抑制されることを確認しており、創薬研究にも有用と考えられる。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (11 results)

All 2021 2020 2019 Other

All Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Impaired phosphorylation of c-Ret causes cerebellar hypoplasia in mice with Hirschsprung disease.2021

    • Author(s)
      Ohgami N, Iizuka A, Hirai H, Yajima I, Iida M, Shimada A, Tsuzuki T, Jijiwa M, Asai N, Takahashi M, Kato M
    • Journal Title

      J Biol Chem

      Volume: - Pages: 100389-100389

    • DOI

      10.1016/j.jbc.2021.100389

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hair graying with aging in mice carrying oncogenic RET2020

    • Author(s)
      Iida M, Tazaki A, Yajima I, Ohgami N, Taguchi N, Goto Y, Kumasaka YM, Prevost-Blondel A, Kono M, Akiyama M, Takahashi M, Kato M
    • Journal Title

      Aging Cell

      Volume: 19(11) Issue: 11

    • DOI

      10.1111/acel.13273

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peptides Containing the MXXCW Motif Inhibit Oncogenic RET Kinase Activity With a Novel Mechanism of Action2020

    • Author(s)
      Takeda K, Kawamoto Y, Nagasaki Y, Okuno Y, Goto Y, Iida M, Yajima I, Ohgami N, Kato M.
    • Journal Title

      Am J Cancer Res.

      Volume: 10 Pages: 336-349

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of mast cell degranulation by melanin.2019

    • Author(s)
      Kawamoto Y, Kondo H, Hasegawa M, Kurimoto C, Ishii Y, Kato C, Botei T, Shinya M, Murate T, Ueno Y, Kawabe M, Goto Y, Yamamoto R, Iida M, Yajima I, Ohgami N, Kato M, Takeda K.
    • Journal Title

      Biochem Pharmacol.

      Volume: 163 Pages: 178-193

    • DOI

      10.1016/j.bcp.2019.02.015

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] A unique system that can sensitively assess the risk of chemical leukoderma by using murine tail skin2019

    • Author(s)
      Iida Machiko、Tazaki Akira、Deng Yuqi、Chen Wei、Yajima Ichiro、Kondo-Ida Lisa、Hashimoto Kazunori、Ohgami Nobutaka、Kato Masashi
    • Journal Title

      Chemosphere

      Volume: 235 Pages: 713-718

    • DOI

      10.1016/j.chemosphere.2019.06.185

    • NAID

      120006777551

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Histological analysis of the skin of Abca1-deleted mice: A potential model for dry skin2019

    • Author(s)
      Deng Yuqi、Ohgami Nobutaka、Iida Machiko、Tazaki Akira、Intoh Atsushi、Kondo-Ida Lisa、Lu Rui、Tsuzuki Toyonori、Yokoyama Shinji、Kato Masashi
    • Journal Title

      Eur J Dermatol

      Volume: 29 Issue: 5 Pages: 549-551

    • DOI

      10.1684/ejd.2019.3621

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Girdin knockout mice exhibit epilepsy accompanied by interneuron migration defect2021

    • Author(s)
      Machiko Iida, Motoki Tanaka, Naoya Asai, Masahide Takahashi, Masato Asai
    • Organizer
      第44回日本神経科学大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Temporal pathological analyses of Girdin/ccdc88a KO mice in which MTLE develops.2020

    • Author(s)
      Machiko Iida, Motoki Tanaka, Yuka Mizutani, Kaichi Yoshizaki, Yoshihito Tokita, Naoya Asai, Masahide Takahashi, Masato Asai
    • Organizer
      第43回日本神経科学学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 全般性強直間代てんかん発作マウスモデルと全自動動画てんかん解析システムの結合2020

    • Author(s)
      Masato Asai, Machiko Iida, Motoki Tanaka, Yuka Mizutani, Kaichi Yoshizaki, Tsuyoshi Takagi, Tokita, Naoya Asai, Masahide Takahashi
    • Organizer
      第43回日本神経科学学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Girdin/ccsc88a KOマウスに発症したてんかん発作2019

    • Author(s)
      Iida M, Tanaka M, Mizutani Y, Yoshizaki K, Tokita Y, Asai N, Takahashi M, Asai M.
    • Organizer
      日本神経科学学会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] 愛知県医療療育総合センター 発達障害研究所

    • URL

      https://www.pref.aichi.jp/addc/eachfacility/hattatsu/index.html

    • Related Report
      2020 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2023-01-30  

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