Pathologcial analysis for mouse model showing dystonia

• Project/Area Number: 24700351
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Niigata University
• Principal Investigator: HORIE Masao 新潟大学, 医歯学系, 講師 (70322716)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ジストニア / ジストニン / マウス / 中枢神経系 / 末梢神経系 / モデルマウス / ｌacZ

Outline of Final Research Achievements

Dystonia is a disorder characterized by involuntary muscle contractions that cause slow repetitive movements, abnormal postures, or both. We had generated a novel Dystonin gene trap (DstGt) mice, in which actin-binding domain-containing isoforms are disrupted. Homozygous DstGt mice showed typical progressive neurological symptoms: severe motor disorders in their limbs and twisted postures. Electromyogram showed abnormal co-contractions of agonist and antagonist muscle in DstGt homozygotes. In histological analyses, abnormal neurofilament accumulation was observed in both peripheral and central nervous system. In order to know the abnormal neural regions possibly affecting the motor disorder in these mice, we mapped the distribution of abnormal neurofilament protein and found that it mainly concentrated in the motor-related neurons, suggesting that they are involved in the abnormal motor phenotype in DstGt.

Research Products

• [Journal Article] Disruption of actin-binding domain-containing Dystonin protein causes dystonia musculorum in mice. (2014)
  • Author(s): Horie, M., Watanabe, K., Bepari, A. K., Nashimoto, J., Araki, K., Sano, H., Chiken, S., Nambu, A., Ono, K., Ikenaka, K., Kakita, A., Yamamura, K. and Takebayashi, H.
  • Journal Title: Eur. J Neurosci. Volume: 40 Issue: 10 Pages: 3458-3471
  • DOI: 10.1111/ejn.12711
  • Peer Reviewed
• [Presentation] Analyses of mouse model showing dystonia with sensory neurodegeneration (2016)
  • Author(s): 堀江正男、竹林浩秀
  • Organizer: 第121回日本解剖学会総会全国学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-27
• [Presentation] Examination for possible involvement of the vestibular and reticular nuclei in the emergence for dystonia-like movements in Dystonin-deficient mice (2015)
  • Author(s): 堀江正男、佐野裕美、知見聡美、小林憲太、小野勝彦、南部篤、竹林浩秀
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸国際会議場・神戸国際展示場（兵庫県神戸市）
  • Year and Date: 2015-07-21
• [Presentation] Histological analysis of the brain in Dystonin-deficient mice (2015)
  • Author(s): Masao Horie, Hiromi Sano, Satomi Chiken, Kenta Kobayashi, Katsuhiko Ono, Atsushi Nambu, Hirohide Takebayashi
  • Organizer: 第120回日本解剖学会
  • Place of Presentation: 神戸国際会議場・展示場
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Dystonin 変異ジストニアモデルマウスにおける ニューロン・グリアの表現型解析 (2015)
  • Author(s): 堀江正男
  • Organizer: 第20回グリアクラブ
  • Place of Presentation: KKRはこだて
  • Year and Date: 2015-01-26 – 2015-01-28
• [Presentation] Examination for possible involvement of the vestibular and reticular nuclei in the emergence for dystonia-like movements in Dystonin-deficient mice (2014)
  • Author(s): Masao Horie, Hiromi Sano, Satomi Chiken, Kenta Kobayashi, Katsuhiko Ono, Atsushi Nambu, Hirohide Takebayashi
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Histological analysis of the brain in Dystonin-deficient mice (2014)
  • Author(s): 堀江正男, 渡辺啓介, 佐野裕美, 梨本 淳一郎, 知見聡美, 南部篤, 小野勝彦, 柿田明美, 竹林浩秀
  • Organizer: 第119回日本解剖学会
  • Place of Presentation: 自治医科大学キャンパス、地域医療研修センターおよび教育・研究棟
• [Presentation] Essential role of actin binding domain-containing Dystonin in the pathogenesis of dystonia musculorum (2013)
  • Author(s): 堀江正男, 渡辺啓介, ベパリ オシム, 梨本 淳一郎, 荒木喜美, 小野勝彦, 池中一裕, 柿田明美, 山村研一,竹林浩秀
  • Organizer: 第37回峠の会
  • Place of Presentation: 福島県耶麻郡猪苗代町中の沢温泉 リゾートインぼなり
• [Presentation] Essential role of actin binding domain-containing Dystonin in the pathogenesis of dystonia musculorum (2013)
  • Author(s): 堀江正男, 渡辺啓介, ベパリ オシム, 竹林浩秀
  • Organizer: 第23回国際形態科学学会
  • Place of Presentation: 新潟市 朱鷺メッセ 新潟コンベンションセンター
• [Presentation] Dystonin遺伝子改変ジストニアモデルマウスにおける原因遺伝子発現領域の解析 (2013)
  • Author(s): 堀江正男、渡辺啓介、Asim K Bepari、荒木善美、小野勝彦、池中一裕、竹林浩秀
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: サンポートホール高松・かがわ国際会議場