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An animal model of Lam bert-Eaton myasthenic syndrome using adeovirus expressing a1A subunit of P/Q-type voltage-gated calcium channel

Research Project

Project/Area Number 15590896
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionNagasaki University

Principal Investigator

MOTOMURA Masakatsu  Nagasaki Univ., Grad.Sch.of Bio M., Lecturer, 大学院・医歯薬学総合研究科, 講師 (70244093)

Co-Investigator(Kenkyū-buntansha) SHIRABE Susumu  Nagasaki Univ., Grad.Sch.of Bio M., Sub professor, 大学院・医歯薬学総合研究科, 助教授 (40264220)
EGUCHI Katumi  Nagasaki Univ., Grad.Sch.of Bio M., Sub professor, 大学院・医歯薬学総合研究科, 教授 (30128160)
YOSHIMURA Toshiro  Nagasaki Univ., Grad.Sch.of Health Sci., Professor, 医学部, 教授 (80182822)
MIZUSAWA Hidehiro  Tokyo Med. & Den.Univ., Professor, 大学院・医歯学総合研究科, 教授 (30144091)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsLambert-Eaton myasthenic syndrome(LEMS) / P / O-type voltage-gated calcium channel (P / O-type VGCC) / α1A subunit / immunization / animal model / in vivo / adenovirus / pHMVCMV6
Research Abstract

The Lambert-Eaton myasthenic syndrome(LEMS) is an autoimmune disorder of neuromuscular transmission in which IgG autoantibodies lead to presynaptic voltage-gated calcium channel(VGCC) loss. As a paraneoplastic disorder, 60% of patients with LEMS have small cell lung carcinoma that express functional VGCCs. A diagnostic radioimmunoassay to detect anti-P/Q-type VGCC antibodies using ^<125>I-ω-conotoxin MVIIC can be detected in 85-95% of LEMS patients. This result suggests that antibodies to P/Q-type calcium channels are the principal pathogenic factor. However, autoantibodies in LEMS are heterogeneous because antibodies against different VGCC subtypes and synaptotagmin have been identified. To clarify the pathogenesis of LEMS, we made a plan of LEMS animal model using adeovirus expressing a1A subunit of P/Q-type voltage-gated calcium channel. In conclusion, we can not make an animal model of LEMS. The reason is that we was not able to make an adenovirus expressing a1A subunit of P/Q-type voltage-gated calcium channel because its molecular size is very huge. Now we are considering another strategy.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (20 results)

All 2005 2004 2003 Other

All Journal Article (16 results) Publications (4 results)

  • [Journal Article] Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenig gravis.2005

    • Author(s)
      H Shiraishi, et al.
    • Journal Title

      Ann Neurol 57(2)

      Pages: 289-293

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenia gravis.2005

    • Author(s)
      H Shiraishi, et al.
    • Journal Title

      Ann Neurol 57(2)

      Pages: 289-293

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenia gravis.2005

    • Author(s)
      Shiraishi H, Motomura M, et al.
    • Journal Title

      Ann Neurol 57(2)

      Pages: 289-293

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Thymic myoid cells as a myasthenogenic antigen and antigen-presentina cells.2004

    • Author(s)
      M Y Matsumoto, et al.
    • Journal Title

      J Neuroimmunol 150

      Pages: 80-87

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Anti-ryanodine receptor antibodies and FK506 in myasthenia gravis.2004

    • Author(s)
      M Takamori, et al.
    • Journal Title

      Neurology 62

      Pages: 1894-1896

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Thymic myoid cells as a myasthenogenic antigen and antigen-presenting cells.2004

    • Author(s)
      M Y Matsumoto, et al.
    • Journal Title

      J Neuroimmunol 150

      Pages: 80-87

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Anti-ryanodine antimodies and FK506 in myasthenia gravis.2004

    • Author(s)
      Takamori M, Moromura M, et al.
    • Journal Title

      Neurology 62(10)

      Pages: 1894-1896

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Thymic myoid cells as a myasthenogenic antigen and antigen-presenting cells.2004

    • Author(s)
      Matsumoto MY, Matsuo H, et al.
    • Journal Title

      J Neuroimmunol 150(1-2)

      Pages: 80-87

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Reduction of P/Q-type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambert-Eaton myasthenic syndrome.2003

    • Author(s)
      T Fukuda, et al.
    • Journal Title

      Ann Neurol 53(1)

      Pages: 21-28

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] What's in the serum of seronegative MG and LEMS?2003

    • Author(s)
      M Motomura, et al.
    • Journal Title

      Neurology 61(2)

      Pages: 277-278

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Paraneoplastic cerebellar degeneration and antibodies to P/Q-type calcium channels.2003

    • Author(s)
      M Motomura, et al.
    • Journal Title

      Ann Neurol 54(2)

      Pages: 277-278

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and Lambert-Eaton myasthenic syndrome.2003

    • Author(s)
      T Nagashima, et al.
    • Journal Title

      Neuropathol 23

      Pages: 230-238

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] 神経因性膀胱を合併し,ステロイド治療後良好な経過を呈したChurg-Strauss症候群の1例2003

    • Author(s)
      藤本武士 他
    • Journal Title

      日本内科学会雑誌 92(2)

      Pages: 131-133

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lambert-Eaton筋無力症候群とスローチャネル症候群2003

    • Author(s)
      本村政勝
    • Journal Title

      神経研究の進歩 47(2)

      Pages: 291-303

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Churg-Strauss syndrome with neurogenic bladder and good recovery after steroid therapy.2003

    • Author(s)
      Fujimoto T, et al.
    • Journal Title

      Nippon Naika Gakkai Zasshi 92(2)

      Pages: 131-133

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Lambert-Eaton myasthenic syndrome and slow channel syndrome.2003

    • Author(s)
      M Motomura, et al.
    • Journal Title

      Advances in Neurological Sciences 47(2)

      Pages: 291-303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Nagashima T, et al.: "Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and Lambent-Eaton myasthenic syndrome"Neuropathology. 23(3). 230-238 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujimoto T, et al.: "Churg-Strauss syndrome with neurogenic bladder and good recovery after steroid therapy"Nippon Naika Gakkai Zasshi. 92(2). 307-309 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsujihata M, et al.: "Effect of myasthenic immunoglobulin G on motor end-plate morphology"J Neurol. 250(1). 75-81 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukuda T, et al.: "Reduction of P/Q-type calcium channels in the postmortem cerebellum of paraneoplastic cerebellar degeneration with Lambent-Eaton myasthenic syndrome"Ann Neurol. 53(1). 21-28 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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