Résumé :
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Communication n°369 The objective was to develop a mouse model for studying the pathophysiology of myasthenia gravis patients with auto-antibodies to MuSK, a tyrosine kinase receptor responsible for clustering of acetylcholine receptors (AChRs) at the neuromuscular junction. Methods. To test the hypothesis that anti-MuSK(+) antibodies might interfere with the clustering of AChRs, we used the mouse flexor digitorum brevis which we exposed to notexin causing a rapid loss of muscle fibres followed by the formation of new junctions on regenerated muscles fibres a few days later. Results. After injections of plasma into the foot sole during two weeks (0.08 ml/day), we found that muscles upon nerve stimulation at 0.01 Hz contracted with about the same force (normalized for direct stimulation of muscle), irrespective whether the mice had been injected with anti-MuSK(+) plasma or plasma from patients without a neuromuscular disease. However, in the presence of 0.35 mM Ca2+ instead of 2 mM the experimental muscles showed a two to three times reduced contraction force relative to that in muscles from control injected mice (P< 0.005, in 2 patients). The half life of 125I after subcutaneous injection of 125I-alphabungarotoxin, was not influenced by anti-MuSK(+) plasma; it was about 2 days shortly after muscle fibre regeneration and 10 days in the period of 10-20 days after notexin. Furthermore, anti-MuSK(+) plasma had no significant effect on the amount of AChRs at 14 days after notexin. It is concluded that while anti-MuSK(+) plasma apparently induces a small change in the synapse it is unlikely that this is due to an effect on the number or turnover of AChRs.
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