Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability.
Lgi1 null mutant mice exhibit myoclonic seizures and CA1 neuronal hyperexcitability.
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DOI：
10.1093/hmg/ddq047
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发表时间：
2010-02
影响因子：
3.5
通讯作者：
Y. E. Yu;Lei Wen;Jeane Silva;Zhongyou Li;K. Head;K. Sossey-Alaoui;A. Pao;L. Mei;J. Cowell
中科院分区：
文献类型：
--
作者：
Y. E. Yu;Lei Wen;Jeane Silva;Zhongyou Li;K. Head;K. Sossey-Alaoui;A. Pao;L. Mei;J. Cowell
人类LGI1与常染色体显性遗传性部分性癫痫(ADPEAF)的易感性有关。然而，LGI1突变如何导致癫痫的机制仍不清楚。我们使用了一种小鼠染色体工程策略，为编码LGI1的基因直系同源基因创造了零突变。从常规的组织病理学分析来看，Lgi1缺失突变小鼠没有表现出总体发育异常。12-18天后，纯合子突变小鼠均出现肌阵挛发作，并伴有快速跳跃和奔跑，随后不久死亡。杂合突变小鼠不会出现癫痫发作。电生理分析表明，通过增加兴奋性神经递质谷氨酸的释放，兴奋性突触传递增强，这为癫痫表型提供了基础。因此，这个小鼠模型为ADPEAF背后的机制提供了新的见解，并为研究LGI1在肌阵挛发作易感性背后的作用机制提供了新的机会。
LGI1 in humans is responsible for a predisposition to autosomal dominant partial epilepsy with auditory features (ADPEAF). However, mechanisms of how LGI1 mutations cause epilepsy remain unclear. We have used a mouse chromosome engineering strategy to create a null mutation for the gene ortholog encoding LGI1. The Lgi1 null mutant mice show no gross overall developmental abnormalities from routine histopathological analysis. After 12-18 days of age, the homozygous mutant mice all exhibit myoclonic seizures accompanied by rapid jumping and running and die shortly thereafter. The heterozygous mutant mice do not develop seizures. Electrophysiological analysis demonstrates an enhanced excitatory synaptic transmission by increasing the release of the excitatory neurotransmitter glutamate, suggesting a basis for the seizure phenotype. This mouse model, therefore, provides novel insights into the mechanism behind ADPEAF and offers a new opportunity to study the mechanism behind the role of LGI1 in susceptibility to myoclonic seizures.