Generation and application of the novel mouse model for Alzheimer's disease

• Project/Area Number: 19689009
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: SAITO Takashi The Institute of Physical and Chemical Research, 神経蛋白制御研究チーム, 研究員 (90360552)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000); Fiscal Year 2009: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2008: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2007: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
• Keywords: アルツハイマー病 / モデルマウス / アミロイド前駆体蛋白 / アミロイドβペプチド / プレセニリン1 / アミロイド前駆体蛋白質(APP) / アミロイドβペプチド(Aβ) / プレセニリン1(PS1) / ノックインマウス / アミロイド前駆体蛋白(APP) / プレセニリン-1

Research Abstract

We generated two lines of the novel mouse model for Alzheimer's disease (AD), amyloid precursor protein (APP) knock-in (KI) mouse and presenilin1(PS1)-KI mouse. Each KI mice has the familial AD mutations. The mice showed relevance phenotypes rather than previous AD model mouse. These mice would be a useful tool for the prevention, the treatment and the drug discovery of AD.

Research Products

• [Journal Article] Interleukin-1β up-regulates TACE to enhance α-cleavage of APP in neurons: resulting in Aβ production. (2008)
  • Author(s): Y. Tachida, K. Nakagawa, T. Saito, T. Saido, T. Honda, Y. Sato, S. Murayama, T. Endo, G. Sakaguchi, A. Kato, S. Kitazume, Y. Hashimoto
  • Journal Title: Journal of Neurochemistry 104 Pages: 1387-1393
  • Peer Reviewed
• [Journal Article] Interleukin-1β up-regulates TACE to enhance α-cleavage of APP in neuron: resulting decrease in Aβ production (2008)
  • Author(s): Yuriko Tachida, et. al.
  • Journal Title: Journal of Neurochemistry 104 Pages: 1387-1393
  • Peer Reviewed
• [Presentation] R278I-プレセニリン1家族性変異による新知見 (2009)
  • Author(s): 斉藤貴志(以下7名)
  • Organizer: 第28回日本認知症学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2009-11-20
• [Presentation] R278I-プレセニリン1家族性変異による新知見～胎生致死とAβ43産生に伴うアミロイド病理の促進～ (2009)
  • Author(s): 斉藤貴志, 以下7名
  • Organizer: 日本認知症学会
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 2009-11-20
• [Presentation] R278I-プレセニリン1変異が持つユニークな機能 (2009)
  • Author(s): 斉藤貴志(以下7名)
  • Organizer: 第82回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] R278I-プレセニリン1変異が持つユニークな機能～胎生致死とAβ43産生に伴うアミロイド病理の促進～ (2009)
  • Author(s): 斉藤貴志, 以下7名
  • Organizer: 日本生化学会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2009-10-24
• [Presentation] The biological effects of R278I-Presenilin-1 familial mutation on γ-secretase activity and amyloid pathology. (2009)
  • Author(s): Takashi Saito(以下7名)
  • Organizer: International Conference for Alzheimer's Disease 2009
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2009-07-15
• [Presentation] The biological effects of R278I-Presenilin-1 familial mutation on γ-secretase activity and amyloid pathology (2009)
  • Author(s): 斉藤貴志, et al
  • Organizer: International conference of Alzheimer's Disease2009
  • Place of Presentation: Wien, Austria
  • Year and Date: 2009-07-15
• [Presentation] The 2nd generation mouse model for Alzheimer's disease. (2008)
  • Author(s): Takashi Saito(以下4名)
  • Organizer: International Conference for Alzheimer's Disease 2008
  • Place of Presentation: Chicago, USA
  • Year and Date: 2008-07-27
• [Presentation] Accelerated Aβ plaque formation by low level expression of presenilin-1 with R278I mutation in knock-in mouse. (2008)
  • Author(s): Takahiro Suemoto, Takashi Saito(以下6名)
  • Organizer: International Conference for Alzheimer's Disease 2008
  • Place of Presentation: Chicago, USA
  • Year and Date: 2008-07-27
• [Presentation] The 2nd generation mouse mpdel for Alzheimer's Disease. (2008)
  • Author(s): Takashi Saito, et al.
  • Organizer: International conference of Alzheimer's Disease2008
  • Place of Presentation: Chicago, USA
  • Year and Date: 2008-07-27
• [Presentation] Accelerated Aβplaque formation by low level expression of Presenilin-1 with R278I mutation in knock-in mouse. (2008)
  • Author(s): T. Suemoto, and T. Saito , et al.
  • Organizer: International conference of Alzheimer's Disease2008
  • Place of Presentation: Chicago, USA
  • Year and Date: 2008-07-27
• [Presentation] R278I変異プレセニリン1ノックインマウスにおけるアミロイドプラーク形成の促進 (2008)
  • Author(s): 末元隆寛、斉藤貴志(以下6名)
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-09
• [Presentation] 次世代型アルツハイマー病モデルマウスの作製及びその解析 (2007)
  • Author(s): 斉藤貴志(以下4名)
  • Organizer: 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 次世代型アルツハイマー病モデルの作製及びその解析 (2007)
  • Author(s): Takashi Saito, et. al
  • Organizer: 日本生化学会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] APP-KI, a novel type mouse, for Alzheimer's disease. (2007)
  • Author(s): Takashi Saito(以下4名)
  • Organizer: The 37 th annual meeting of the Society for Neuroscience
  • Place of Presentation: SanDiego, USA
  • Year and Date: 2007-11-07
• [Presentation] APP-KI mice, a novel type mouse model, for Alzheimer's disease (2007)
  • Author(s): Takashi Saito, et. al
  • Organizer: Society for neuroscience
  • Place of Presentation: SanDiego, USA
  • Year and Date: 2007-11-07
• [Remarks] 所属研究室ホームページ
  • URL: http://www.brain.riken.go.jp/labs/pns/index/html
• [Remarks] 理研一般公開2009(2009年4月18日)
• [Remarks] 理研一般公開2008(2008年4月19日)
• [Patent(Industrial Property Rights)] アルツハイマー病モデル動物およびその用途 (2006)
  • Inventor(s): 西道隆臣、斉藤貴志、岩田修永、高野二郎、末元隆寛
  • Industrial Property Rights Holder: 西道隆臣、斉藤貴志、岩田修永、高野二郎、末元隆寛
  • Filing Date: 2006-06-20