| Project/Area Number |
17590883
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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 BioM.Sci., Lecturer, 大学院医歯薬学総合研究科, 講師 (70244093)
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| Co-Investigator(Kenkyū-buntansha) |
EGUCHI Katumi Nasgasaki Univ., Grad.Sch.of BioM.Sci., Professor, 大学院医歯薬学総合研究科, 教授 (30128160)
FUKUDOME Takayasu Nagasaki Medical Center of Neurology., Subprofessor, 大学院医歯薬学総合研究科, 助教授 (30380976)
YOSHIMURA Toshiro Nasgasaki Univ., Grad.Sch.of Health Sci., Professor, 大学院医歯薬学総合研究科, 教授 (80182822)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | myasthenia gravis / muscle-specific tyrosine kinase MuSK / AChR / autoantibody / target antigen / animal model / immunization / rat |
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| Research Abstract |
Heading : The aim of this study is to investigate the pathogenesis and characteristics of muscle-specific tyrosine kinase (MuSK) antibody in experimental autoimmune myasthenia gravis (EAMG) rat.
Background : Some of generalized seronegative MG patients have antibodies (Ab) against MuSK. But it is not clear how the Ab cause myasthenic symptoms. We investigated the pathogenesis of MuSK Ab using rat.
Methods : Female Lewis rats, aged 8 weeks were inoculated twice in multiple intradermal sites, either MuSK protein (10-100μg) in complete Freund' s adjuvant (CFA) and Bordetella pertussis as co-adjuvant or the controls. Soluble mouse MuSK-6xHis protein was purified from HEK293.
Results : Th3 weights of MuSK-immunized rats were lower than those of the control rats. The titers of antibodies to MuSK raised markedly compared with those of the controls. The electrophysiological examination using diaphragm was negative. The quantity of AChR and MuSK at the endplates of limb muscles were reduced in MuSK-immunized rats, compared with those of the control rats. The morphological changes, AChR-declustering muscle fibers have appeared in the MuSK-immunized rat (EDL, white muscle > soleus, red muscle).
Conclusions : Our results suggest that anti-MuSK antibodies in MuSK-immunized rat may down-regulate MuSK and AChR, lead to the morphological changes in motor endplates. Further investigations will draw the conclusion whether MuSK Ab may be pathogenic or not.
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