Guidelines for preclinical animal and cellular models of MuSK-myasthenia gravis.
Guidelines for preclinical animal and cellular models of MuSK-myasthenia gravis.
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MuSK 重症肌无力临床前动物和细胞模型指南。
DOI：
10.1016/j.expneurol.2014.12.013
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发表时间：
2015
期刊：
影响因子：
5.3
通讯作者：
Vincent A.
中科院分区：
文献类型：
--
作者：
Phillips WE;Christadoss P;Losen M;Punga A;Shigemoto K;Vershuuren J;Vincent A.
肌肉特异性酪氨酸激酶（MuSK）自身抗体是一种重症肌无力（MG）的标志，可以挑战神经学家和实验学家。临床疾病可能难以有效治疗。MuSK自身抗体以几种方式影响神经肌肉接头。当添加到培养的肌肉细胞中时，MuSK抗体分散乙酰胆碱受体簇。用MuSK主动免疫的实验动物产生MuSK自身抗体和肌无力。虚弱与突触后乙酰胆碱受体数量减少、微小终板电位和终板电位振幅降低以及神经肌肉传递失败有关。在注射来自MuSK自身抗体阳性的MG患者（MuSK-MG）的IgG的小鼠中也发现了类似的损伤。主动和被动模型已经开始揭示MuSK抗体破坏神经肌肉接头处突触功能的机制，并且在开发MuSK-MG的疗法中应该是有价值的。然而，为患者转化为新的和改进的治疗方法需要不太繁琐的程序，但适合检查MuSK功能的不同方面和潜在治疗的效果。研究的设计、实施和分析应得到认真考虑，并以透明的方式报告。在这里，我们回顾了从MuSK-MG的动物和培养模型中学到的东西，并为实验设计和研究的进行提供指导，包括样本量的确定，随机化，结果参数和客观数据分析的注意事项。这些原则也可能与越来越多的其他抗体介导的疾病，现在认识到。
Muscle-specific tyrosine kinase (MuSK) autoantibodies are the hallmark of a form of myasthenia gravis (MG) that can challenge the neurologist and the experimentalist. The clinical disease can be difficult to treat effectively. MuSK autoantibodies affect the neuromuscular junction in several ways. When added to muscle cells in culture, MuSK antibodies disperse acetylcholine receptor clusters. Experimental animals actively immunized with MuSK develop MuSK autoantibodies and muscle weakness. Weakness is associated with reduced postsynaptic acetylcholine receptor numbers, reduced amplitudes of miniature endplate potentials and endplate potentials, and failure of neuromuscular transmission. Similar impairments have been found in mice injected with IgG from MG patients positive for MuSK autoantibody (MuSK-MG). The active and passive models have begun to reveal the mechanisms by which MuSK antibodies disrupt synaptic function at the neuromuscular junction, and should be valuable in developing therapies for MuSK-MG. However, translation into new and improved treatments for patients requires procedures that are not too cumbersome but suitable for examining different aspects of MuSK function and the effects of potential therapies. Study design, conduct and analysis should be carefully considered and transparently reported. Here we review what has been learnt from animal and culture models of MuSK-MG, and offer guidelines for experimental design and conduct of studies, including sample size determination, randomization, outcome parameters and precautions for objective data analysis. These principles may also be relevant to the increasing number of other antibody-mediated diseases that are now recognized.