An animal model of Lam bert-Eaton myasthenic syndrome using adeovirus expressing a1A subunit of P/Q-type voltage-gated calcium channel

Lambert-Eaton肌无力综合征（LEMS）是一种神经肌肉传递的自身免疫性疾病，其中IgG自身抗体导致突触前电压门控钙通道（VGCC）丢失。作为一种副肿瘤性疾病，60%的LEMS患者患有表达功能性VGCC的小细胞肺癌。在<125>85-95%的LEMS患者中可以检测到使用β I-ω-芋螺毒素MVIIC检测抗P/Q型VGCC抗体的诊断性放射免疫测定。这一结果表明，P/Q型钙通道的抗体是主要的致病因素。然而，LEMS中的自身抗体是异质性的，因为已经鉴定了针对不同VGCC亚型和突触结合蛋白的抗体。为了阐明LEMS的发病机制，我们利用表达P/Q型电压门控性钙通道α 1A亚单位的腺病毒建立了LEMS动物模型。因此，我们不能建立LEMS的动物模型.原因是我们不能制造表达P/Q型电压门控钙通道a1 A亚单位的腺病毒，因为其分子尺寸非常大。现在我们正在考虑另一种策略。

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.