Deciphering the pathogenesis of neuropsychiatric disease using Depdc5 conditional KO mice

• Project/Area Number: 16H06765
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Laboratory animal science
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Ishida Saeko 東京医科歯科大学, 難治疾患研究所, 助教 (50777927)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: てんかん / 自閉症 / 脳神経疾患 / 遺伝子 / 動物 / 神経疾患 / 実験動物学

Outline of Final Research Achievements

The comorbidity between epilepsy and psychosis is well known, but the underlying common pathogenesis remains unclear. Recently, mutations of DEP　domain　containing protein 5 （DEPDC5）gene have been reported from patients with various type of epilepsies and/or psychiatric disorders including autism spectrum disorder (ASD). It suggests that understanding the function of Depdc5 provides new insights into pathogenesis of both diseases.
Depdc5 is reported as an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), a central regulator of cell growth, proliferation and protein synthesis. However, the function in brain is still unknown. Because homozygous Depdc5 knockout rodents are embryonic lethal, in this study, we conditionally deleted Depdc5 in brain of mice, and characterized their phenotypes.

Research Products

• [Journal Article] Depdc5 knockdown causes mTOR-dependent motor hyperactivity in zebrafish (2018)
  • Author(s): de Calbiac H, Dabacan A, Marsan E, Tostivint H, Devienne G, Ishida S, Leguern E, Baulac S, Muresan RC, Kabashi E, Ciura S.
  • Journal Title: Annals of Clinical and Translational Neurology Volume: - Issue: 5 Pages: 510-523
  • DOI: 10.1002/acn3.542
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 焦点性てんかん原因遺伝子DEPDC5 (2017)
  • Author(s): 石田 紗恵子
  • Organizer: 日本薬理学会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-17
  • Invited
• [Presentation] 焦点性てんかん原因遺伝子、DEPDC5 KOラットの解析 (2017)
  • Author(s): 石田 紗恵子
  • Organizer: 関西実験動物研究会
  • Place of Presentation: 京都
  • Year and Date: 2017-03-03
  • Invited
• [Presentation] てんかんと遺伝子 (2017)
  • Author(s): 石田 紗恵子
  • Organizer: 日本てんかん学会
  • Invited