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

使用表达 P/Q 型电压门控钙通道 a1A 亚基的腺病毒建立 Lam bert-Eaton 肌无力综合征动物模型

• 批准号: 15590896
• 负责人: MOTOMURA Masakatsu
• 金额: $ 2.18万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590896/
• 关键词: Lambert-Eaton myasthenic syndrome(LEMS); P; O-type voltage-gated calcium channel (P; O-type VGCC); α1A subunit; immunization; animal model; in vivo; adenovirus; pHMVCMV6

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.

兰伯特 - 原始肌无力综合征（LEMS）是神经肌肉传播的自身免疫性疾病，其中IgG自身抗体导致突触前电压门控钙通道（VGCC）损失。作为一种副肿瘤疾病，有60％的LEM患者患有小细胞肺癌，表达功能性VGCC。可以在85-95％的LEMS患者中检测到使用 ^<125> i-ω-持续毒素MVIIC检测抗P/Q-Type VGCC抗体的诊断放射免疫测定法。该结果表明对P/Q-Type钙通道的抗体是主要致病因素。但是，LEM中的自身抗体是异质性的，因为已经鉴定出针对不同VGCC亚型和突触的抗体抗体。为了阐明LEM的发病机理，我们使用表达P/Q型电压门控钙通道的A1A亚基制定了LEMS动物模型的计划。总之，我们无法制作LEM的动物模型。原因是我们无法制作表达P/Q型电压门控钙通道A1A亚基的腺病毒，因为其分子大小非常大。现在我们正在考虑另一种策略。

项目成果

Anti-ryanodine antimodies and FK506 in myasthenia gravis.

重症肌无力中的抗兰尼定抗体和 FK506。

• 发表时间: 2004
• 期刊: Neurology 62(10)
• 作者: Takamori M;Moromura M;et al.
• 通讯作者: et al.

Paraneoplastic cerebellar degeneration and antibodies to P/Q-type calcium channels.

副肿瘤性小脑变性和 P/Q 型钙通道抗体。

• 发表时间: 2003
• 期刊: Ann Neurol 54(2)
• 作者: M Motomura;et al.
• 通讯作者: et al.

Nagashima T, et al.: "Anti-Hu paraneoplastic syndrome presenting with brainstem-cerebellar symptoms and Lambent-Eaton myasthenic syndrome"Neuropathology. 23(3). 230-238 (2003)

Nagashima T 等人：“Anti-Hu 副肿瘤综合征表现为脑干小脑症状和 Lambent-Eaton 肌无力综合征”神经病理学。

Thymic myoid cells as a myasthenogenic antigen and antigen-presentina cells.

胸腺肌样细胞作为肌无力抗原和抗原呈递细胞。

• 发表时间: 2004
• 期刊: J Neuroimmunol 150
• 作者: M Y Matsumoto;et al.
• 通讯作者: et al.

Tsujihata M, et al.: "Effect of myasthenic immunoglobulin G on motor end-plate morphology"J Neurol. 250(1). 75-81 (2003)

Tsujihata M 等人：“肌无力免疫球蛋白 G 对运动终板形态的影响”J Neurol。