The creation of novel treatment and testing for developmental disorders based on the mechanisms of a developmental disorder model accompanying social abnormality.

• Project/Area Number: 23591501
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Gunma University
• Principal Investigator: MITSUI Shinichi 群馬大学, 保健学研究科, 教授 (20295661)
• Co-Investigator(Kenkyū-buntansha): GAMOH Keji 高知大学, 総合科学系, 教授 (90204817)
• Co-Investigator(Renkei-kenkyūsha): YURI Kazunari 高知大学, 医歯学系, 教授 (10220534) ; OSAKO Yoji 高知大学, 医歯学系, 准教授 (40335922)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 知的発達障害 / プロテアーゼ / 社会行動 / motopsin / neurotrypsin / sez-6 / prss12 / 精神遅滞 / 発達障害 / Neurotrypsin / PRSS12 / テトラサイクリン系

Research Abstract

The principal investigator has reported that the loss of motopsin, a serine protease in the brain, enhances social behaviors. In this research, we analyzed the effects of motopsin and sez-6, which was identified as a motopsin-binding protein, on the cell morphology when they were transfected in neuroblastoma cells. The results suggested that these proteinases coordinately modulate the morphology of neuronal cells. Further, we showed a possibility that serine proteases in the brain ordinarily modulate social behaviors, since the mice lacking tissue plasminogen activator, another protease in the brain, showed enhanced social anxiety in behavioral tests.

Research Products

• [Journal Article] Mental retardation-related protease, motopsin (prss12), binds to the BRICHOS domain of the integral membrane protein 2a. (2014)
  • Author(s): S. Mitsui, Y. Osako, K. Yuri
  • Journal Title: Cell Biology International Volume: 38 Issue: 1 Pages: 117-123
  • DOI: 10.1002/cbin.10164
  • Peer Reviewed
• [Journal Article] A mental retardation gene, motopsin/prss12, modulates cell morphology by interaction with seizure-related gene 6. (2013)
  • Author(s): S. Mitsui, C. Hidaka, M. Furihata, Y. Osako, K. Yuri
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 436 Issue: 4 Pages: 638-644
  • DOI: 10.1016/j.bbrc.2013.04.112
  • Peer Reviewed
• [Journal Article] 出会いに支えられて ―発達障害の分子機構研究への道のり― (2013)
  • Author(s): 三井 真一
  • Journal Title: The KITAKANTO Medical Journal Volume: 63 Pages: 63-64
  • NAID: 130003368230
• [Journal Article] Dermokine-β impairs ERK signaling through direct binding to GRP78 (2012)
  • Author(s): Kiyoshi Higashi, Minoru Hasegawa, Chikako Yokoyama, Taro Tachibana, Shinichi Mitsui, Koichi Saito
  • Journal Title: FEBS Letter Volume: 586 Issue: 16 Pages: 2300-2305
  • DOI: 10.1016/j.febslet.2012.06.022
  • Peer Reviewed
• [Journal Article] 唾液試料を用いた自閉症スペクトラム障害のメタボローム解析 (2011)
  • Author(s): 蒲生啓司,須貝一貴
  • Journal Title: 高知大学学術研究報告 Volume: 60 Pages: 241-252
  • NAID: 40019230713
  • URL: http://hdl.handle.net/10126/4848
• [Presentation] Serine proteases modulating social behavior (2013)
  • Author(s): Mitsui, S.
  • Organizer: Advanced Micro Device Engineering (AMDE2013)
  • Place of Presentation: Kiryu, Japan
  • Year and Date: 2013-12-19
• [Presentation] Function of seizure related gene 6 (sez 6)in neurite elongation and branching (2013)
  • Author(s): Hidaka, C., Mitsui, S.
  • Organizer: Advanced Micro Device Engineering (AMDE2013)
  • Place of Presentation: Kiryu, Japan
  • Year and Date: 2013-12-19
• [Presentation] A serine protease in the brain modulates social behaviors (2013)
  • Author(s): Mitsui, S.
  • Organizer: Brain and Health Informatics (BHI 2013)
  • Place of Presentation: Maebashi, Japan
  • Year and Date: 2013-10-30
• [Presentation] 唾液試料を用いる自閉症スペクトラム障害のメタボローム解析 (2013)
  • Author(s): 蒲生啓司,須貝一貴
  • Organizer: 第61回質量分析総合討論会
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2013-09-10
• [Presentation] Tissue type plasminogen activator modulates social anxiety (2013)
  • Author(s): Mitsui, S., Nakamura, K., Takabe,A., Shimizu, F., Okada, K., Matsuo, O.
  • Organizer: 日本神経科学学会(Neuro2014)
  • Place of Presentation: 京都
  • Year and Date: 2013-06-21
• [Presentation] Serine proteases modulating social behavior. (2013)
  • Author(s): S. Mitsui
  • Organizer: 5th International Conference on Advanced Micro-Device Engineering
  • Place of Presentation: Kiryu (Japan)
• [Presentation] Function of seizure-related gene (sez-6) in neurite elongation and branching. (2013)
  • Author(s): C. Hidaka, S. Mitsui
  • Organizer: 5th International Conference on Advanced Micro-Device Engineering
  • Place of Presentation: Kiryu (Japan)
• [Presentation] A serine protease in the brain modulates social behaviors. (2013)
  • Author(s): S. Mitsui
  • Organizer: 2013 International conferences on Brain and Health Informatics
  • Place of Presentation: Meabashi (Japan)
  • Invited
• [Presentation] Tissue-type plasminogen activator modulates social anxiety. (2013)
  • Author(s): S. Mitsui, K. Nakamura, A. Takabe, F. Shimizu, K. Okada, O. Matsuo
  • Organizer: Neuro2013（第36回日本神経科学大会，第56回日本神経化学会大会，第23回日本神経回路学会大会）
  • Place of Presentation: 京都
• [Presentation] 脳内プロテオリシスの破綻による精神発達障害の発症機構 (2012)
  • Author(s): 三井真一
  • Organizer: 第59回北関東医学会総会
  • Place of Presentation: 前橋市
  • Year and Date: 2012-09-28
  • Invited
• [Presentation] Metabolomic Analysis of Saliva of Autism Spectrum Disorders (2012)
  • Author(s): Gamoh, K., Sugai, K.
  • Organizer: 19th International Mass Spectrometry Conference
  • Place of Presentation: Kyoto International Conference Centre, Kyoto
  • Year and Date: 2012-09-20
• [Presentation] 脳内プロテオリシスの破綻による精神発達障害の発症機構 (2012)
  • Author(s): 三井 真一
  • Organizer: 第５９回北関東医学会総会
  • Place of Presentation: 群馬大学刀城会館（前橋市）
  • Invited
• [Presentation] Modulation of neurite extension and branching by the interaction of a mental retardation gene, motopsin/neurotrypsin, and seizure related gene (sez)6 (2011)
  • Author(s): Hidaka, C., Mitsui, S., Yuri, K.
  • Organizer: Neuroscience 2011
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2011-11-13
• [Presentation] 精神遅滞原因遺伝子motopsin/neurotrypsinとSeizure related gene (Sez)6との相互作用によるニューロンの形態の制御 (2011)
  • Author(s): 三井真一,由利和也
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-09-16
• [Presentation] 唾液試料を用いた自閉症のメタボロミクス研究(2) (2011)
  • Author(s): 蒲生啓司,須貝一貴
  • Organizer: 日本分析化学会第60年会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-09-16
• [Presentation] 精神遅滞原因遺伝子motopsin/neurotrypsinとSeizure related gene (Sez)-6との相互作用によるニューロンの形態の制御 (2011)
  • Author(s): 三井 真一、由利和也
  • Organizer: 第34回日本神経科学大会
  • Place of Presentation: パシフィコ横浜（神奈川県）
• [Presentation] Modulation of neurite extension and branching by the interaction of a mental retardation gene, motopsin/neurotrypsin, and seizure related gene (sez)-6. (2011)
  • Author(s): Chiharu Hidaka, Shinichi Mitsui, Kazunari Yuri
  • Organizer: Neuroscience 2011
  • Place of Presentation: ワシントンDC（米国）