Analysis of ALS2 function in motor neurons form common marmoset

• Project/Area Number: 21700397
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Kitasato University (2011); Tokai University (2009-2010)
• Principal Investigator: ASAKO Otomo 北里大学, 理学部, 講座研究員 (50535226)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ALS / ALS2 / 筋萎縮性側索硬化症2型 / マーモセット / 運動ニューロン / ES細胞

Research Abstract

To understand the molecular mechanisms underlying neuronal dysfunctionand celldeath caused by loss of ALS2, we tried togenerateALS2 deficient cellular model using marmoset ES cells. We succeededin determining ALS2 sequence in marmoset, and cloned siRNA-mediated ALS2down-regulatedmarmoset ES cells. By differentiating theseES clones, we will analyzethe function of ALS2 in primate motor neuron.

Research Products

• [Journal Article] Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases (2012)
  • Author(s): 大友麻子、潘麗、秦野伸二
  • Journal Title: Neurology Research International Volume: (In press)
  • URL: http://www.hindawi.com/journals/nri/
• [Journal Article] Different human copper-zinc superoxide dismutase mutants, SOD1G93A and SOD1H46R, exert distinct harmful effects on gross phenotype in mice (2012)
  • Author(s): 潘麗、吉井康弘、大友麻子、小川温子、岩崎泰雄、秦野伸二
  • Journal Title: PLoS One Volume: 7巻、3号
  • URL: http://dx.doi.org/10.1371/journal.pone.0033409
• [Journal Article] Different Human Copper-Zinc Superoxide Dismutase Mutants, SOD1G93A and SOD1H46R, Exert Distinct Harmful Effects on Gross Phenotype in Mice (2012)
  • Author(s): Lei Pan
  • Journal Title: PLoS One Volume: 7巻 Issue: 3 Pages: e33409-e33409
  • DOI: 10.1371/journal.pone.0033409
  • Peer Reviewed
• [Journal Article] Defective relocalization of ALS2/alsin missense mutants to Rac1-induced macropinosomes accounts for loss of their cellular function and leads to disturbed amphisome formation (2011)
  • Author(s): 大友麻子、國田竜太、鈴木(宇都宮)恭子、池田譲衛、秦野伸二
  • Journal Title: FEBS Lett Volume: 585巻、5号 Pages: 730-736
  • URL: http://dx.doi.org/10.1016/j.febslet.2011.01.045
• [Journal Article] Loss of glial fibrillary acidic protein marginally accelerates disease progression in a SOD1(H46R) transgenic mouse model of ALS (2011)
  • Author(s): 吉井康弘、大友麻子、潘麗、大塚正人、秦野伸二
  • Journal Title: Neuroscience Research Volume: 70巻、3号 Pages: 321-329
  • URL: http://dx.doi.org/10.1016/j.neures.2010.06.004
• [Journal Article] Loss of glial fibrillary acidic protein marginally accelerates disease progression in a SOD1(H46R) transgenic mouse model of ALS (2011)
  • Author(s): Yasuhiro Yoshii
  • Journal Title: Neuroscience Research Volume: 30巻 Issue: 3 Pages: 321-329
  • DOI: 10.1016/j.neures.2011.03.006
  • Peer Reviewed
• [Journal Article] Defective relocalization of ALS2/alsin to Rac1-induced macropinosomes accounts for loss of its cellular function and leads to disturbed amphisome formation (2011)
  • Author(s): Asako Otomo
  • Journal Title: Amyotrophic Lateral Sclerosis Volume: 12巻 Issue: sup1 Pages: 134-134
  • DOI: 10.3109/17482968.2011.615526
  • Peer Reviewed
• [Journal Article] Defective relocalization of ALS2/alsin missense mutants to Rac1-induced macropinosomes accounts for loss of their cellular function and leads to disturbed amphisome formation (2011)
  • Author(s): 大友麻子
  • Journal Title: FEBS Letters Volume: 585 Pages: 730-736
  • Peer Reviewed
• [Journal Article] Genetic background and gender effects on gross phenotypes in congenic lines of ALS2/alsin-deficient mice (2011)
  • Author(s): 秦野伸二
  • Journal Title: Neuroscience Research Volume: 68 Pages: 730-736
  • Peer Reviewed
• [Journal Article] Genetic background and gender effects on gross phenotypes in congenic lines of ALS2/alsin-deficient mice (2010)
  • Author(s): 秦野伸二、吉井康弘、大友麻子、國田竜太、鈴木(宇都宮)恭子、潘麗、角田茂、岩崎泰雄、岩倉洋一郎、池田譲衛
  • Journal Title: Neuroscience Research Volume: 68巻、2号 Pages: 131-136
  • URL: http://dx.doi.org/10.1016/j.neures.2010.06.004
• [Journal Article] Lower serum lipid levels are related to respiratory impairment in patients with ALS (2010)
  • Author(s): 吉井康弘、秦野伸二、大友麻子、川邉清一、池田憲、岩崎泰雄
  • Journal Title: Neurology Volume: 74巻、24号 Pages: 2027-2027
  • URL: http://www.neurology.org
• [Journal Article] Loss of ALS2/Alsin exacerbates motordysfunction in a SOD1-expressing mouse ALS model by disturbing endolysosomal trafficking (2010)
  • Author(s): 秦野伸二、大友麻子、國田竜太、鈴木(宇都宮)恭子、赤塚明、小池正人、青木正志、内山安男、糸山泰人、池田譲衛
  • Journal Title: PLoS One Volume: 5巻、3号
  • URL: http://dx.doi.org/10.1371/journal.pone.0009805
• [Journal Article] Natural history of young-adult amyotrophic lateral sclerosis (2009)
  • Author(s): 吉井康弘、秦野伸二、大友麻子, 鈴木恭子、池田憲、池田譲衛、岩崎泰雄
  • Journal Title: Neurology Volume: 73巻、8号 Pages: 648-649
  • URL: http://www.neurology.org
• [Journal Article] Rac1-induced macropinosomal and endosomal localization of ALS2 underlies the pathogenesis for motor neuron diseases caused by missense mutations in the ALS2 gene (2009)
  • Author(s): 大友麻子
  • Journal Title: Amyotrophic Lateral Sclerosis 10(Suppl.1) Pages: 42-42
  • Peer Reviewed
• [Presentation] Defective relocalization of ALS2/alsin to Rac1-induced macropinosomes accounts for loss of its cellular function and leads to disturbed amphisome formation (2011)
  • Author(s): 大友麻子, 國田竜太, 鈴木(宇都宮)恭子、池田譲衛、秦野伸二
  • Organizer: 22nd INTERNATIONAL SYMPODIUM on ALS/MND
  • Place of Presentation: Sidney, Australia
• [Presentation] Defective relocalization of ALS2/alsin to Rac1-induced macropinosomes accounts for loss of its cellular function and leads to disturbed amphisome formation (2011)
  • Author(s): 大友麻子
  • Organizer: 第22回ALS/MND国際シンポジウム
  • Place of Presentation: オーストラリア・シドニー
• [Presentation] Rab5 and its activator ALS regulate autophagosome maturation and autophagoly (2010)
  • Author(s): 大友麻子, 國田竜太, 鈴木(宇都宮)恭子、池田譲衛、秦野伸二
  • Organizer: 21st INTERNATIONAL SYMPODIUM on ALS/MND
  • Place of Presentation: orland, U. S. A
• [Presentation] Rab5 and its activator ALS2 regulate autophagosome maturation and autophagolysosome-mediated protein degradation (2010)
  • Author(s): 大友麻子
  • Organizer: 第21回ALS/MND国際シンポジウム
  • Place of Presentation: アメリカ合衆国・オーランド
• [Presentation] Rac1-induced macropinosomal and endosomal localization of ALS2 underlies the pathogenesis for motor neuron diseases caused by missense mutations in the ALS2 gene (2009)
  • Author(s): 大友麻子
  • Organizer: 20th INTERNATIONAL SYMPODIUM on ALS/MND
  • Place of Presentation: ドイツ(ベルリン)
  • Year and Date: 2009-12-09
• [Presentation] Loss Of Rac1-induced macropinosomal and endosomal localization of ALS2 underlies the pathogenesis for motor neuron diseases caused by missense mutations in the ALS2 gene (2009)
  • Author(s): 大友麻子, 國田竜太, 鈴木(宇都宮)恭子、池田譲衛、秦野伸二
  • Organizer: 20th INTERNATIONAL SYMPODIUM on ALS/MND
  • Place of Presentation: Berlin, Germany