A research for dissecting molecular pathogenesis of SCA31.

• Project/Area Number: 21591072
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: ISHIKAWA Kinya 東京医科歯科大学, 医学部附属病院, 講師 (30313240)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: ゲノム / 拡散 / 脳神経疾患 / マイクロアレー / プロテオーム / 遺伝子 / 脳 / 神経変性疾患 / 難病 / 実験動物 / 遺伝子改変 / RNA / 脊髄小脳変性症 / 小脳 / 神経疾患 / トランスジェニックマウス / 神経細胞

Research Abstract

We performed basic research for three years(FY2009-2011) and achieved a success to generate SCA31 model mice. We introduced a BAC(bacterial artificial chromosome) clone, derived from a SCA31 affected individual, into mice fertilized eggs. We obtained 9 lines positive for the gene of interest. Four different lines were finally established. The SCA31 mutation was confirmed transcribed in the transgenic mice. These achievements are crucial for the future understanding of pathogenesis as well as establishment of treatments in SCA31.

Research Products

• [Journal Article] Reduced brain-derived neurotrophic factor(BDNF) mRNA expression and presence of BDNF-immunoreactive granules in the spinocerebellar ataxia type 6(SCA6) cerebellum (2012)
  • Author(s): Takahashi M, Ishikawa K, Sato N, Obayashi M, Niimi Y, Ishiguro T, Yamada M, Toyoshima Y, Takahashi H, Kato T, Takao M, Murayama M, Mori O, Eishi Y, Mizusawa H.
  • Journal Title: Neuropathology Volume: (in press)
• [Journal Article] Prevalence of inositol 1, 4, 5-triphosphate receptor type 1 gene(ITPR1) deletion, the mutation forspinocerebellar ataxia type 15(SCA15), in Japan screened by gene dosage (2012)
  • Author(s): Obayashi M, Ishikawa K, Izumi Y, Takahashi M, Niimi Y, Sato N, Onodera O, Kaji R, Nishizawa M, Mizusawa H.
  • Journal Title: J Hum Genet Volume: 57(3) Pages: 202-206
• [Journal Article] Reduced brain-derived neurotrophic factor (BDNF) mRNA expression and presence of BDNF-immunoreactive granules in the spinocerebellar ataxia type 6 (SCA6) cerebellum (2012)
  • Author(s): Takahashi M, Ishikawa K, Sato N, Obayashi M, Niimi Y, Ishiguro T, Yamada M, Toyoshima Y, Takahashi H, Kato T, Takao M, Murayama M, Mori O, Eishi Y, Mizusawa H
  • Journal Title: Neuropathology Volume: (in press) Issue: 6 Pages: 593-603
  • DOI: 10.1111/j.1440-1789.2012.01302.x
  • Peer Reviewed
• [Journal Article] Prevalence of inositol 1,4,5-triphosphate receptor type 1 gene (ITPR1) deletion, the mutation for spinocerebellar ataxia type 15 (SCA15), in Japan screened by gene dosage (2012)
  • Author(s): Obayashi M, Ishikawa K, Izumi Y, Takahashi M, Niimi Y, Sato N, Onodera O, Kaji R, Nishizawa M, Mizusawa H
  • Journal Title: J Hum Genet Volume: 57(3) Issue: 3 Pages: 202-206
  • DOI: 10.1038/jhg.2012.5
  • Peer Reviewed
• [Journal Article] The chromosome 16q-linked autosomal dominant cerebellar ataxia (16q-ADCA^*) : A newly identified degenerative ataxia in Japan showing peculiar morphological changes of the Purkinje cell (2012)
  • Author(s): Ishikawa K, Mizusawa H
  • Journal Title: Neuropathology
  • Peer Reviewed
• [Journal Article] Pentanucleotide repeats at the spinocerebellar ataxia type 32(SCA31) locus in Caucasians (2011)
  • Author(s): Ishikawa K, D rr A, Klopstock T, M ller S, De Toffol B, Vighetto A, Marelli C, Wichmann HE, Illig T, Niimi Y, Sato N, Amino T, Stevanin G, Brice A, Mizusawa H.
  • Journal Title: Neurology Volume: 77(20) Pages: 1853-1855
• [Journal Article] Pentanucleotide repeats at the spinocerebellar ataxia type 32 (SCA31) locus in Caucasians (2011)
  • Author(s): Ishikawa K, Durr A, Klopstock T, Muller S, De Toffol B, Vighetto A, Marelli C, Wichmann HE, Illig T, Niimi Y, Sato N, Amino T, Stevanin G, Brice A, Mizusawa H
  • Journal Title: Neurology Volume: 77(20) Pages: 1853-1855
  • Peer Reviewed
• [Journal Article] The chromosome 16q-linked autosomal dominant cerebellar ataxia(16q-ADCA*): A newly identified degenerative ataxia in Japan showing peculiar morphological changes of the Purkinje cell (2010)
  • Author(s): Ishikawa K, Mizusawa H.
  • Journal Title: Neuropathology Volume: 30(5) Pages: 490-494
• [Journal Article] The carboxy-terminal fragment of alpha1A calcium channel preferentially aggregates in the cytoplasm of human spinocerebellar ataxia type 6 Purkinje cells (2010)
  • Author(s): Ishiguro T, Ishikawa K, Takahashi M, Obayashi M, Amino T, Sato N, Sakamoto M, Fujigasaki H, Tsuruta F, Dolmetsch R, Arai T, Sasaki H, Nagashima K, Kato T, Yamada M, Takahashi H, Hashizume Y, Mizusawa H.
  • Journal Title: Acta Neuropathol Volume: 119(4) Pages: 447-464
• [Journal Article] The chromosome 16q-linked autosomal dominant cerebellar ataxia (16q-ADCA*) : A newly identified degenerative ataxia in Japan showing peculiar morphological changes of the Purkinje cell. (2010)
  • Author(s): Ishikawa K, Mizusawa H.
  • Journal Title: Neuropathology Volume: (Epub)
  • Peer Reviewed
• [Journal Article] The carboxy-terminal fragment of alphalA calcium channel preferentially aggregates in the cytoplasm of human spino-cerebellar ataxia type 6 Purkinje cells. (2010)
  • Author(s): Ishiguro T, Ishikawa K, Takahashi M, Obayashi M, Amino T, Sato N, Sakamoto M, Fujigasaki H, Tsuruta F, Dolmetsch R, Arai T, Sasaki H, Nagashima K, Kato T, Yamada M, Takahashi H, Hashizume Y, Mizusawa H.
  • Journal Title: Acta Neuropathologica Volume: 119(4) Pages: 447-464
  • Peer Reviewed
• [Journal Article] The chromosome 16q-linked autosomal dominant cerebellar ataxia (16q-ADCA^*) : A newly identified degenerative ataxia in Japan showing peculiar morphological changes of the Purkinje cell. (2010)
  • Author(s): Ishikawa K, Mizusawa H.
  • Journal Title: Neuropathology Volume: (Epub)
  • Peer Reviewed
• [Journal Article] The carboxy-terminal fragment of alpha1A calcium channel preferentially aggregates in the cytoplasm of human spino-cerebellar ataxia type 6 Purkinje cells. (2010)
  • Author(s): Ishiguro T, Ishikawa K, Takahashi M, Obayashi M, Amino T, Sato N, Sakamoto M, Fujigasaki H, Tsuruta F, Dolmetsch R, Arai T, Sasaki H, Nagashima K, Kato T, Yamada M, Takahashi H, Hashizume Y, Mizusawa H.
  • Journal Title: Acta Neuropathologica Volume: 119(4) Pages: 447-464
  • Peer Reviewed
• [Journal Article] Spinocerebellar ataxia type 31 is associated with "inserted" penta-nucleotide repeats containing(TGGAA) n (2009)
  • Author(s): Sato N, Amino T, Kobayashi K, Asakawa S, Ishiguro T, Tsunemi T, Takahashi M, Matsuura T, Flanigan KM, Iwasaki S, Ishino F, Saito Y, Murayama S, Yoshida M, Hashizume Y, Takahashi Y, Tsuji S, Shimizu N, Toda T, Ishikawa K, Mizusawa H.
  • Journal Title: Am J Hum Genet Volume: 85(5) Pages: 554-557
• [Presentation] 細胞モデルを用いた脊髄小脳失調症31型(SCA31)の病態探索 (2011)
  • Author(s): 新美祐介,佐藤望,網野猛志,高橋真,大林正人,石黒太郎,石川欽也,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: 2011-05-18
• [Presentation] 教育講演:「脊髄小脳変性症」 (2010)
  • Author(s): 石川欽也, 網野猛志, 佐藤望, 新美祐介, 融 衆太, 水澤英洋
  • Organizer: 日本人類遺伝学会第55回大会
  • Place of Presentation: さいたま市
  • Year and Date: 2010-10-28
• [Presentation] Prominent respiratory muscle involvement in adPEO with POLG1 mutation. (2010)
  • Author(s): Ishikawa K., et al.
  • Organizer: The 15th International Congress of the World Muscle Society.
  • Place of Presentation: 熊本市
  • Year and Date: 2010-10-15
• [Presentation] Prominent respiratory muscle involvement in adPEO with POLG1 mutation. (2010)
  • Author(s): Ishikawa K., et al.
  • Organizer: The 15^<th> International Congress of the World Muscle Society.
  • Place of Presentation: 熊本市
  • Year and Date: 2010-10-15
• [Presentation] SCA6原因の同定から治療法の開発へ (2010)
  • Author(s): 渡瀬啓,石川欽也,水澤英洋
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-22
• [Presentation] シンポジウム16.「Neurodegenerative diseases and RNA.」SCA31 (2010)
  • Author(s): 石川欽也、網野猛志、佐藤望,新美祐介,融衆太,水澤英洋
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-22
• [Presentation] シンポジウム「神経変性疾患とRNA」演題:SCA31 (2010)
  • Author(s): 石川欽也, 網野猛志, 佐藤望, 新美祐介, 融衆太, 水澤英洋
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-22
• [Presentation] シンポジウム「神経変性疾患とRNA」演題:SCA31 (2010)
  • Author(s): 石川欽也、網野猛志、佐藤望、新美祐介、融衆太、水澤英洋
  • Organizer: 第51回 日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-22
• [Presentation] シンポジウム9-1ポリグルタミン病への分子生物学的アプローチ.「脊髄小脳変性症への分子生物学的アプローチ」 (2009)
  • Author(s): 石川欽也,石黒太郎,高橋真,佐藤望,網野猛志,新美祐介,水澤英洋
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-22
• [Presentation] Tsien RW, Zoghbi HY. SCA6ノックインマウス表現型の経時的検討 (2009)
  • Author(s): 渡瀬啓, Barrett CF,宮崎太輔、海野敏紀、石川欽也、笠井沙由美、渡辺雅彦、水澤英洋
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-20
• [Presentation] 50周年記念標本提示「日本が世界に発信したあの疾患」本邦で同定された新しい脊髄小脳変性症16q-ADCA-その特異的Purkinje細胞変性 (2009)
  • Author(s): 石川欽也,水澤英洋
  • Organizer: 第50回日本神経病理学会総会学術研究会
  • Place of Presentation: 高松
• [Presentation] 「脊髄小脳変性症の分子病態」シンポジウム4-S-5-3(シンポジウム4.こころと神経:「神経変性疾患の病態と治療(脊髄小脳変性症を含む)」
  • Author(s): 石川欽也、水澤英洋
  • Organizer: 第28回日本医学会総会
• [Book] 脊髄小脳失調症31型(SCA31). Annual Review神経 (2011)
  • Author(s): 石川欽也,佐藤望,網野猛志,新美祐介,融衆太,水澤英洋
• [Book] 遺伝性脊髄小脳変性症.雑誌「内科」特集「内科疾患の診断基準病型分類・重症度」 (2010)
  • Author(s): 石川欽也、水澤英洋
• [Book] 不随意運動.雑誌「内科」特集「内科疾患の診断基準病型分類・重症度」 (2010)
  • Author(s): 石川欽也、水澤英洋
  • Total Pages: 1398
• [Book] 脊髄小脳変性症の分類と治療.鈴木則宏・編「からだの科学」神経内科の病気のすべて (2010)
  • Author(s): 石川欽也、水澤英洋
  • Publisher: 日本評論社
• [Book] 脊髄小脳変性症. In :落合滋之監修森田明夫、吉澤利弘編集,「脳神経疾患ビジュアルブック」 (2009)
  • Author(s): 石川欽也
  • Publisher: 学研
• [Book] 多系統萎縮症. In :落合滋之監修森田明夫、吉澤利弘編集,「脳神経疾患ビジュアルブック」 (2009)
  • Author(s): 石川欽也
  • Publisher: 学研