Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK)
Myasthenia gravis induced in mice by immunization with the recombinant extracellular domain of rat muscle-specific kinase (MuSK)
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DOI：
10.1016/j.jneuroim.2006.03.016
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发表时间：
2006-06-01
影响因子：
3.3
通讯作者：
Hoch, Werner
中科院分区：
文献类型：
--
作者：
Jha, Smita;Xu, Kaiping;Hoch, Werner
重症肌无力(MG)主要由抗乙酰胆碱受体自身抗体(AChR)引起。在10-15%的MG患者中，这种抗体是检测不到的，但许多人都有抗肌肉特异性激酶(Musk)抗体。在H-2(A)、H-2(B)、H-2(Bm12)和H-2(D)小鼠体内注射重组大鼠麝香胞外区。某些菌株表现出运动性疲劳、震颤、体重减轻，有些在注射2-3次后死亡。复合肌肉动作电位随着低频重复神经刺激的增加而降低。微型终板电位降低，提示终板功能性AChR数量减少。肌无力血清抑制集聚蛋白诱导的C2C12肌管AChR聚集。结论：抗麝香单抗可诱发MG，其机制可能与阻断集聚蛋白信号通路有关。(C)2006年，爱思唯尔出版。
Myasthenia gravis (MG) is mostly caused by anti-acetylcholine receptor (AChR) auto-antibodies (Abs). Such Abs are undetectable in 10-15% of MG patients, but many have anti-muscle-specific kinase (MuSK) Abs. We injected recombinant rat-MuSK extracellular domain in H-2(a), H-2(b), H-2(bm12) and H-2(d) mice. Certain strains exhibited exercise-induced fatigue, tremors, weight loss, and some died after 2-3 injections. Compound muscle action potentials showed decrement with low-frequency repetitive nerve stimulation. Miniature endplate potentials decreased, suggesting lower numbers of endplates functional AChRs. Myasthenic sera inhibited agrin-induced AChR aggregation in C2C12 myotubes. Conclusion: Anti-MuSK Abs induce MG, which might also result from blocking the agrin-signaling pathway. (c) 2006 Published by Elsevier B.V