Utilizing the ADAMTS13-mutant mice to identify modifiers of thrombotic thrombocytopenic purpura

• Project/Area Number: 20790687
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Hematology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: BANNO Fumiaki National Cardiovascular Center Research Institute, 脈管生理部, 室員 (00373514)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 遺伝子 / 酵素 / 生体分子 / 動物 / ADAMTS13 / フォンビルブランド因子 / 血栓性血小板減少性紫斑病 / 血小板 / モデルマウス

Research Abstract

ADAMTS13は血小板接着蛋白質フォンビルブランド因子の断片化を担う血漿プロテアーゼである。我々はADAMTS13研究におけるモデル動物として、ADAMTS13完全欠損マウス、C末端ドメイン欠損マウスを樹立した。本研究ではまず、ADAMTS13変異マウスの血小板血栓形成能を解析し、ADAMTS13の完全欠損は過剰血栓形成傾向をもたらすこと、C末端ドメインは高ずり応力下血小板血栓形成を効率よく抑制するために必須となることを明らかにした。さらに、マウス中大脳動脈閉塞モデルを用いて、脳虚血再灌流障害に及ぼすADAMTS13の影響を解析した結果、ADAMTS13は再灌流後の微小循環障害を抑制することが明らかとなった。

Research Products

• [Journal Article] ADAMTS13のC端末ドメイン欠損マウス (2010)
  • Author(s): 坂野史明, 小亀浩市
  • Journal Title: 血栓と循環 18 Pages: 4-7
• [Journal Article] ADAMTS13 gene deletion aggravates ischemic brain damage: A possible neuroprotective role of ADAMTS13 by ameliorating post-ischemic hypoperfusion (2010)
  • Author(s): Fujioka M, Hayakawa K, Mishima K, Kunizawa A, Irie K, Higuchi S, Nakano T, Muroi C, Fukushima H, Sugimoto M, Banno F, Kokame K, Miyata T, Fujiwara M, Okuchi K, Nishio K
  • Journal Title: Blood 115 Pages: 1650-1653
  • Peer Reviewed
• [Journal Article] The function of ADAMTS13 in thrombogenesis in vivo: insights from mutant mice (2010)
  • Author(s): Banno F, Chauhan AK, Miyata T
  • Journal Title: Int J Hematol 91 Pages: 30-35
  • NAID: 10026110458
  • Peer Reviewed
• [Journal Article] The function of ADAMTS13 in thrombogenesis in vivo : insights from mutant mice (2010)
  • Author(s): Fumiaki Banno
  • Journal Title: Int J Hematol 91 Pages: 30-35
  • NAID: 10026110458
  • Peer Reviewed
• [Journal Article] ADAMTS13 gene deletion aggravates ischemic brain damage : A possible neuroprotective role of ADAMTS13 by ameliorating post-ischemic hypoperfusion (2010)
  • Author(s): Masayuki Fujioka
  • Journal Title: Blood 115 Pages: 1650-1653
  • Peer Reviewed
• [Journal Article] ADAMTS13のC端末ドメイン欠損マウス (2010)
  • Author(s): 坂野史明
  • Journal Title: 血栓と循環 18 Pages: 4-7
• [Journal Article] The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation (2009)
  • Author(s): Banno F, Chauhan AK, Kokame K, Yang J, Miyata S, Wagner DD, Miyata T
  • Journal Title: Blood 113 Pages: 5323-5329
  • Peer Reviewed
• [Journal Article] 血栓形成制御におけるADAMTS13とそのC末端ドメインの生理的意義 (2009)
  • Author(s): 坂野史明, 小亀浩市, 奥田智彦, 本田繁則, 宮田茂樹, 加藤恒, Chauhan AK, 冨山佳昭, Wagner DD, 宮田敏行
  • Journal Title: JSPP News Letter 23 Pages: 22-23
• [Journal Article] The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation (2009)
  • Author(s): Fumiaki Banno
  • Journal Title: Blood 113 Pages: 5323-5329
  • Peer Reviewed
• [Journal Article] 血栓形成制御におけるADAMTS13とそのC末端ドメインの生理的意義 (2009)
  • Author(s): 坂野史明
  • Journal Title: JSPP News Letter 23 Pages: 22-23
• [Journal Article] The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation (2009)
  • Author(s): Fumiaki Banno
  • Journal Title: Blood (in press)
  • Peer Reviewed
• [Presentation] 低用量テルミサルタンはRegulator of G protein signaling-2 (RGS2)欠損マウスの高血圧性血管障害を改善する-Rgs2遺伝子多型診断と降圧薬選択の可能性について- (2009)
  • Author(s): 松本幸子
  • Organizer: 第32回日本高血圧学会総会
  • Place of Presentation: 大津プリンスホテル(大津市)
  • Year and Date: 2009-10-02
• [Presentation] Protective property of ADAMTS13 in a mouse-model of ischemic stroke (2009)
  • Author(s): Kenji Nishio
  • Organizer: The International Society on Thrombosis and Haemostasis XXII Congress
  • Place of Presentation: Boston Convention & Ezhibition Center (Boston, USA)
  • Year and Date: 2009-07-15
• [Presentation] Imaging analysis of platelet thrombus formation in Adamts 13-mutantmice (2009)
  • Author(s): Fumiaki Banno
  • Organizer: The International Society on Thrombosis and Haemostasis XXII Congress
  • Place of Presentation: Boston Convention & Exhibition Center (Boston, USA)
  • Year and Date: 2009-07-13
• [Presentation] Intra-vital imaging analysis of platelet adhesion to vascular wall in ADAMTS13 KO mice (2009)
  • Author(s): Miroslaw Rybaltowski
  • Organizer: 第32回日本血栓止血学会学術集会
  • Place of Presentation: 北九州国際会議場(北九州市)
  • Year and Date: 2009-06-06
• [Presentation] ADAMTS13の神経保護作用-脳虚血再灌流障害マウスモデルを用いて- (2009)
  • Author(s): 西尾健治
  • Organizer: 第32回日本血栓止血学会学術集会
  • Place of Presentation: 北九州国際会議場(北九州市)
  • Year and Date: 2009-06-06
• [Presentation] 低用量テルミサルタンはRegulator of G protein signaling-2(RGS2)欠損マウスの高血圧性血管障害を改善する-Rgs2遺伝子多型診断と降圧薬選択の可能性について- (2009)
  • Author(s): 松本幸子, 神出計, 坂野史明, 河野雄平, 宮田敏行
  • Organizer: 第32回日本高血圧学会総会
  • Place of Presentation: 大津プリンスホテル
• [Presentation] Imaging analysis of platelet thrombus formation in Adamts13-mutant mice (2009)
  • Author(s): Banno F, Chauhan AK, Kokame K, Yang J, Miyata S, Wagner DD, Miyata T
  • Organizer: The International Society on Thrombosis and Haemostasis XXII Congress
  • Place of Presentation: Boston Convention & Exhibition Center, USA
• [Presentation] Protective property of ADAMTS13 in a mouse-model of ischemic stroke (2009)
  • Author(s): Nishio K, Fujioka M, Hayakawa K, Mishima K, Fujiwara M, Banno F, Kokame K, Miyata T, Shida Y, Sugimoto M, Ueyama T, Fukushima H, Okuchi K
  • Organizer: The International Society on Thrombosis and Haemostasis XXII Congress
  • Place of Presentation: Boston Convention & Exhibition Center, USA
• [Presentation] Intra-vital imaging analysis of platelet adhesion to vascular wall in ADAMTS13 KO mice (2009)
  • Author(s): Miroslaw Rybaltowski, 鈴木優子, 田中晶, 坂野史明, 宮田敏行, 浦野哲盟
  • Organizer: 第32回日本血栓止血学会学術集会
  • Place of Presentation: 北九州国際会議場
• [Presentation] ADAMTS13の神経保護作用-脳虚血再灌流障害マウスモデルを用いて- (2009)
  • Author(s): 西尾健治, 藤岡政行, 福島英賢, 坂野史明, 小亀浩市, 宮田敏行, 植山徹, 志田泰明, 杉本充彦, 奥地和夫
  • Organizer: 第32回日本血栓止血学会学術集会
  • Place of Presentation: 北九州国際会議場
• [Presentation] ADAMTS13 gene deletion aggravates ischemic brain damage (2008)
  • Author(s): Kenji Nishio
  • Organizer: 50th ASH Annual Meeting and Exposition
  • Place of Presentation: San Francisco
  • Year and Date: 2008-12-08
• [Presentation] Intra-vital imaging analysis of platelet adhesion to injured vascular wall through von Willebrand factor (2008)
  • Author(s): Miroslaw Rybaltowski
  • Organizer: 第55回中部生理学会
  • Place of Presentation: 長久手町
  • Year and Date: 2008-10-18
• [Presentation] ADAMTS13による脳虚血再灌流障害抑制効果 (2008)
  • Author(s): 西尾健治
  • Organizer: 第36回日本救急医学会学術集会
  • Place of Presentation: 札幌市
  • Year and Date: 2008-10-14
• [Presentation] 生体内での血小板血栓形成制御におけるADAMTS13とそのC末端ドメインの重要性 (2008)
  • Author(s): 坂野史明
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 京都市
  • Year and Date: 2008-10-11
• [Presentation] Clinical implications of ADAMTS-13 polymorphisms (2008)
  • Author(s): Toshiyuki Miyata
  • Organizer: The 5th Asian-Pacific Congress on Thrombosis and Hemostasis
  • Place of Presentation: Singapore
  • Year and Date: 2008-09-19
• [Presentation] 血栓形成制御におけるADAMTS13とそのC末端ドメインの生理的意義 (2008)
  • Author(s): 坂野史明
  • Organizer: 第13回病態と治療におけるプロテアーゼとインヒビター学会学術集会
  • Place of Presentation: 豊中市
  • Year and Date: 2008-08-22
• [Presentation] ADAMTS13 gene deletion aggravates ischemic brain damage (2008)
  • Author(s): Nishio K, Fujioka M, Hayakawa K, Mishima K, Fujiwara M, Banno F, Kokame K, Miyata T, Shida Y, Sugimoto M, Fukushima H, Okuchi K
  • Organizer: 50th ASH Annual Meeting and Exposition
  • Place of Presentation: Moscone Center, USA
• [Presentation] Intra-vital imaging analysis of platelet adhesion to injured vascular wall through von Willebrand factor (2008)
  • Author(s): Rybaltowski M, Mogami H, Suzuki Y, Ihara H, Banno F, Miyata T, Urano T
  • Organizer: 第55回中部生理学会
  • Place of Presentation: 愛知医科大学
• [Presentation] ADAMTS13による脳虚血再灌流障害抑制効果 (2008)
  • Author(s): 西尾健治, 藤岡政行, 福島英賢, 坂野史明, 小亀浩市, 宮田敏行, 奥地和夫
  • Organizer: 第36回日本救急医学会学術集会
  • Place of Presentation: ロイトン札幌
• [Presentation] 生体内での血小板血栓形成制御におけるADAMTS13とそのC末端ドメインの重要性 (2008)
  • Author(s): 坂野史明, Anil K. Chauhan, 小亀浩市, Denisa D. Wagner, 宮田敏行
  • Organizer: 第70回日本血液学会総会
  • Place of Presentation: 国立京都国際会館
• [Presentation] Clinical implications of ADAMTS-13 polymorphisms (2008)
  • Author(s): Miyata T, Kokame K, Banno F, Shin Y, Akiyama M
  • Organizer: The 5th Asian-Pacific Congress on Thrombosis and Hemostasis
  • Place of Presentation: Grand Copthorne Waterfront Hotel, Singapore
• [Presentation] 血栓形成制御におけるADAMTS13とそのC末端ドメインの生理的意義 (2008)
  • Author(s): 坂野史明, 小亀浩市, 奥田智彦, 本田繁則, 宮田茂樹, 加藤恒, Anil K. Chauhan、冨山佳昭, Denisa D. Wagner, 宮田敏行
  • Organizer: 第13回病態と治療におけるプロテアーゼとインヒビター学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター
• [Book] Biology of an antithrombotic factor-ADAMTS13, Recent Advances in Thrombosis and Hemostasis 2008 (2008)
  • Author(s): Banno F, Miyata T
  • Publisher: Springer
• [Book] Recent Advances in Thrombosis and Hemostasis 2008 (2008)
  • Author(s): Fumiaki Banno
  • Publisher: Springer