Generation and analysis of mice model for Alexander disease

• Project/Area Number: 17390109
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Gunma University
• Principal Investigator: GOMI Hiroshi Gunma University, 生体調節研究所, 准教授 (90293240)
• Project Period (FY): 2005 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥13,820,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥1,620,000); Fiscal Year 2008: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2007: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2006: ¥2,900,000 (Direct Cost: ¥2,900,000); Fiscal Year 2005: ¥3,900,000 (Direct Cost: ¥3,900,000)
• Keywords: Alexander病 / グリア線維性酸性タンパク質 / 反応性グリオーシス / アストログリア / GFAP / 病態モデルマウス

Research Abstract

Alexander病の原因遺伝子であるグリア線維性酸性タンパク質(GFAP)がどのようしてアストログリアの形態異常に関わっているのかを解明するため、GFAP欠損細胞の反応特性をプリオン感染時に誘導される反応性グリオーシスを指標に解析を行った。その結果、GFAP欠損下でも、アストログリアの膨化、GFAP以外のフィラメントタンパク質であるビメンチンの発現上昇といった反応性グリオーシスが誘導されることを見出し、細胞の膨化程度と突起伸長度が野生型に比べ有意に減少していた。また、細胞の増殖形態を反映すると思われるPired cells形成の顕著な亢進を見いだし、反応性グリオーシスにおけるGFAPの役割を解明した

Research Products

• [Journal Article] Docking is not a prerequisite but a temporal constraint for fusion of secretory granules (2008)
  • Author(s): Kasai K, Fujita T, Gomi H, Izumi T
  • Journal Title: Traffic 9 Pages: 1191-1203
  • Peer Reviewed
• [Journal Article] Exophilin4/Slp2-a targets glucagon granules to the plasma embrane through unique Ca^<2+>-inhibitory phospholipid- binding activity of the C2A domain (2007)
  • Author(s): Yu M, Kasai K, Nagashima K, 他6名
  • Journal Title: Molecular Biology of the Cell 18(2) Pages: 688-696
  • Peer Reviewed
• [Journal Article] Rab27b is expressed in a wide range of exocytic cells and involved in the delivery of secretory granules near the plasma membrane (2007)
  • Author(s): Gomi H, Mori K, Itohara S, Izumi T
  • Journal Title: Molecular Biology of the Cell 18(11) Pages: 4377-4386
  • Peer Reviewed
• [Journal Article] Secretory vesicle docking to the plasma membrane : molecular mechanism and functional significance (2007)
  • Author(s): Izumi T, Kasai K, Gomi H
  • Journal Title: Diabetes Obesity and Metabolism 9(2) Pages: 109-117
  • Peer Reviewed
• [Journal Article] Exophilin4/Slp2-a targets glucagon granUles to the plasma membrane through unique Ca^2+-inhibitory phospholipid-binding activity of the C2Adomain (2007)
  • Author(s): Yu, M., Kasai, K., Nagashima, K., Torh, S., Yokota-Hashimoto, H., Okamoto, K., Takeuchi, T., Gomi, H., Izumi, T.
  • Journal Title: Molecular Biology of the Cell 18 Pages: 688-696
  • Peer Reviewed
• [Journal Article] Rab27b is expressed in a wide range of exocytic cells and involved in the delivery of secretory granules near the plasma membrane (2007)
  • Author(s): Gomi, H., Mori, K., Itohara, S., Izumi, T.
  • Journal Title: Molecular Biology of the Cell 18 Pages: 4377-4386
  • Peer Reviewed
• [Journal Article] Secretory vesicle docking to the plasma Inembrane:molecUIar mechani (2007)
  • Author(s): Izumi, T., Kasai, K., Gomi, H.
  • Journal Title: Diabetes Obesity Metabolism 9(spl.2) Pages: 109-117
  • Peer Reviewed
• [Journal Article] Chromosome 2 locus Nidd5 has a potent effect on adiposity in the TSOD mouse (2006)
  • Author(s): Mizutani S, Gomi H, Hirayama I, Izumi T
  • Journal Title: Mammalian Genome 17(5) Pages: 375-384
  • Peer Reviewed
• [Journal Article] Granuphilin is activated by SREBP-1c and involved in impaired insulin secretion in diabetic mice (2006)
  • Author(s): Kato T, Shimano H, 他11名
  • Journal Title: Cell Metabolism 4(2) Pages: 143-154
  • Peer Reviewed
• [Journal Article] Enhanced hippocampal neurodegeneration after traumatic or kinate excitotoxicity in GFAP-null mice (2006)
  • Author(s): Otani N, Nawashiro H, Fukui S, Shima K, Gomi H, Brenner M
  • Journal Title: Journal of Clinical Neuroscience 13(9) Pages: 934-938
  • Peer Reviewed
• [Journal Article] Enhanced hippocampal neurodegeneration after traumatic or kinate excitotoxicity in GFAP-null mice (2006)
  • Author(s): Otani, N., Nawashiro, H., Fukui, S., Shima K., Gomi, H., Brenner,M.
  • Journal Title: Journal of Clinical Neuroscience 13 (9) Pages: 934-938
• [Journal Article] Granuphilin molecularly docks insulin granules to the fusion machinery (2005)
  • Author(s): Gomi H, Mizutani S, Kasai K, Itohara S, Izumi T
  • Journal Title: Journal of Cell Biology 171(1) Pages: 99-109
  • Peer Reviewed
• [Journal Article] Functional analysis of Rab27a effector granuphilin in insulin secretion (2005)
  • Author(s): Izumi T, Gomi H, Torii S
  • Journal Title: Methods in Enzymology : GTPases Regulating Menmbrane Targeting and Fusion 403(18) Pages: 216-229
  • Peer Reviewed
• [Presentation] インスリン分泌顆粒の開口放出におけるRab27aおよびそのエフェクターGranuphilinの役割 (2008)
  • Author(s): 藤田卓二
  • Organizer: 第51回日本糖尿病学会年次学術集会
  • Place of Presentation: 東京
• [Presentation] Exophilin4/Slp2-a targets glucagon granules to the plasma membrane through unique Ca^<2+>-inhibitory phospholipids-binding activity of the C2A domain (2007)
  • Author(s): Kasai K
  • Organizer: The 8th Servier-IGIS Symposium
  • Place of Presentation: France
• [Presentation] Exophilin4/Slp2-a targets glucagon granules to the plasma membrane through unique Ca^<2+>-inhibitory phospholipid-binding activity of the C2A domain (2007)
  • Author(s): Kasai K
  • Organizer: 第40回日本発生生物学会・第59回日本細胞生物学会合同大会
  • Place of Presentation: 福岡
• [Presentation] Exophilin4/Slp2-a targetsglucagon granules to the plasma membrane throughunique Ca2^+-inhibitory phospholipid-binding activity of the C2A domain (2007)
  • Author(s): Kasai, K., YU, M., Gomi, H., Izumi, T.
  • Organizer: 第40回日本発生生物学会・第59回日本細胞生物学会合同大会
  • Place of Presentation: 福岡国際会議場
• [Presentation] 肥満を伴う2型糖尿病モデルマウスTSODにおける脂肪重量に関わる遺伝子領域の解析 (2006)
  • Author(s): 水谷伸
  • Organizer: 第20回糖尿病動物研究会
  • Place of Presentation: 東京
  • Year and Date: 2006-02-09
• [Presentation] Rab27a mediates the tight docking of insulin granules onto the plasma mambrane during glucose stimulation (2005)
  • Author(s): Kasai K
  • Organizer: The 58th Annual Meeting of Japan Society for Cell Biology
  • Place of Presentation: Omiya
• [Remarks]
  • URL: http://www.imcr.gunma-u.ac.jp/lab/molend/
• [Remarks]
  • URL: http://imcr.showa.gunma-u.ac.jp/
• [Remarks]
  • URL: http://imcr.showa.gunma-u.ac.jp/