Establishment for rat model of sporadic amyotrophic lateral sclerosis

• Project/Area Number: 22890051
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Neurology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: OHKUBO Takuya 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (90587461)
• Co-Investigator(Renkei-kenkyūsha): YOKOTA Takanori 東京医科歯科大学, 大学院・医歯学総合研究科脳神経病態学, 教授 (90231688) ; UCHIHARA Toshiki 東京都医学総合研究所, 脳病理形態研究室, 室長 (10223570)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,068,000 (Direct Cost: ¥2,360,000、Indirect Cost: ¥708,000); Fiscal Year 2011: ¥1,469,000 (Direct Cost: ¥1,130,000、Indirect Cost: ¥339,000); Fiscal Year 2010: ¥1,599,000 (Direct Cost: ¥1,230,000、Indirect Cost: ¥369,000)
• Keywords: 筋萎縮性側索硬化症(ALS) / ラットモデル / TDP-43 / 筋萎縮性側索硬化症 / AAV

Research Abstract

Amyotrophic lateral sclerosis(ALS) is a fatal neurodegenerative disease characterized by progressive motor paresis. Recently transactive response DNA-binding protein 43(TDP-43) was newly identified as one of the targeted protein of sporadic ALS, however, their significance has not been fully elucidated. We succeeded in establishment for rat model of sporadic ALS by the method of overexpressing wild-type of human TDP-43 in spinal cords of rats by injecting adeno-associated virus vector into their cervical cords. Our animal models will provide a valuable tool for studying the pathogenesis of sporadic ALS.

Research Products

• [Journal Article] Non-human primate model of ALS with cytoplasmic mislocalizaion of TDP-43. Brain (2012)
  • Author(s): Uchida A, Sasaguri H, Kimura N, TajiriM, Ono F, Ohkubo T, Sakaue F, Kanai K, Hirai T, Sano T, Shibuya K, Kobayashi M, Ueno T, Yamamoto M, Kubodera T, Tomori M, Sakaki K, Enomoto M, HiraiY, Yasutomi Y, Mochizuki H, Uchihara T, Kuwabara S, Mizusawa H, Yokota T.
  • Volume: 135
  • Pages: 833-46
• [Journal Article] Canregional spreading of ALS motor symptoms be explained by prion-like propagation (2012)
  • Author(s): Kanouchi T, Ohkubo T, Yokota T.
  • Journal Title: J Neurol Neurosurg Psychiatry
• [Journal Article] Non-human primate model of amyotrophic lateral sclerosis with cytoplasmic mislocalization of TDP-43 (2012)
  • Author(s): Uchida A, Sasaguri H, Enomoto M, (18番目), et al
  • Journal Title: Brain Volume: 135 Issue: 3 Pages: 833-46
  • DOI: 10.1093/brain/awr348
  • Peer Reviewed
• [Journal Article] Can regional spreading of ALS motor symptoms be explained by prion-like propagation? (2012)
  • Author(s): Kanouchi T, Ohkubo T, Yokota T
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: (in press)
  • Peer Reviewed
• [Journal Article] プリオン病とパーキンソン病 (2011)
  • Author(s): 大久保卓哉, 水澤英洋
  • Journal Title: Frontier in Parkinson Disease Volume: 4 Pages: 196-200
• [Journal Article] プリオン病とパーキンソン病 (2011)
  • Author(s): 大久保卓哉、水澤英洋
  • Journal Title: Frontier in Parkinson Disease Volume: 4(4) Pages: 196-200
• [Presentation] TDP-43過剰発現による孤発性ALSモデルの作製 (2011)
  • Author(s): 横田隆〓,内田あずさ,笹栗弘貴,田尻美緒,佐野達彦,内原俊記,大久保卓哉,水澤英洋
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-19
• [Presentation] 孤発性筋委縮性側索硬化症のラットモデル作製(第2報) (2011)
  • Author(s): 大久保卓哉,田尻美緒,須永史子,平井高志,澁谷和幹,金井数明,桑原聡,水澤英洋,横田隆〓.
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-18
• [Presentation] 上肢完全麻痺を示した孤発性筋委縮性側索硬化症における脊髄前角細胞でのTDP-43の細胞内局在 (2011)
  • Author(s): 佐野達彦,大久保卓哉,上野智美,内田あずさ,内原俊記,水澤英洋,横田隆〓.
  • Organizer: 第52回日本神経学会学術大会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-05-18
• [Presentation] Non-human primate model of ALS with cytoplasmic mislocalization of wild-type TDP-43 (2011)
  • Author(s): Ohkubo T, Uchida A, Sasaguri H, Kimura N, Tajiri M, Kubodera T, Uchihara T, Mizusawa H, Yokota T.
  • Organizer: The 34^<th> Annual Meeting of Japan Neuroscience Society
  • Place of Presentation: Yokohama
• [Presentation] The truncation and phosphorylation of TDP-43 is not prerequisite for motoneuronal degeneration in non-human primate model of amyotrophic lateral sclerosis (2011)
  • Author(s): Tajiri M, Sakaue F, Ohkubo T, UchidaA, Sasaguri H, Kimura N, Mizusawa H, Yokota T.
  • Organizer: The 34^<th> Annual Meeting of Japan Neuroscience Society
  • Place of Presentation: Yokohama
• [Presentation] Non-human primate model of ALS with cytoplasmic mislocalization of wild-type TDP-43 (2011)
  • Author(s): Ohkubo T, Uchida A, Sasaguri H, Kimura N, Tajiri M, Kubodera T, Uchihara T, Mizusawa H, Yokota T
  • Organizer: The 34^<th> Annual Meeting of Japan Neuroscience Society
  • Place of Presentation: Yokohama, Japan
• [Presentation] The truncation and phosphorylation of TDP-43 is not prerequisite for motoneuronal degeneration in non-human primate model of amyotrophic lateral sclerosis (2011)
  • Author(s): Tajiri M, Sakaue F, Ohkubo T, Uchida A, Sasaguri H, Kimura N, Mizusawa H, Yokota T
  • Organizer: The 34^<th> Annual Meeting of Japan Neuroscience Society
  • Place of Presentation: Yokohama, Japan
• [Remarks]
  • URL: http://www.tmd.ac.jp/press-release/20120118/index.html
• [Remarks]
  • URL: http://www.tmd.ac.jp/press-release/20120118/index.html