2004 Fiscal Year Final Research Report Summary
An animal model of Lam bert-Eaton myasthenic syndrome using adeovirus expressing a1A subunit of P/Q-type voltage-gated calcium channel
| Project/Area Number |
15590896
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Nagasaki University |
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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)
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| 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)
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| Project Period (FY) |
2003 – 2004
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| Keywords | Lambert-Eaton myasthenic syndrome(LEMS) / P / O-type voltage-gated calcium channel (P / O-type VGCC) / α1A subunit / immunization / animal model / in vivo / adenovirus / pHMVCMV6 |
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| 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.
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