Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability
Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability
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DOI：
10.1046/j.1471-4159.2000.0750028.x
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发表时间：
2000-07-01
影响因子：
4.7
通讯作者：
Sasai, H
中科院分区：
文献类型：
--
作者：
Watanabe, H;Nagata, E;Sasai, H
良性新生儿惊厥（BFNC）是一种常见的特发性癫痫，具有常染色体显性遗传。最近，通过定位克隆鉴定出两个新的电压依赖性钾通道基因 KCNQ2 和 KCNQ3 与 BFNG 相关。这些基因产物的异四聚体形成M通道并调节神经元电兴奋性的阈值。我们通过基因打靶破坏小鼠 KCNQ2 基因，以研究 KCNQ2 与癫痫之间的关系。纯合子幼崽（KCNQ2 -/-）在出生后几小时内因肺不张而死亡，尽管它们的发育在形态上正常，但肺不张并不是由于癫痫发作的状态。杂合子小鼠的 KCNQ2 表达降低，并对癫痫发作诱导剂戊四唑表现出超敏反应。这些数据表明，KCNQ2 表达的减少可能会导致 CNS 过度兴奋，这就是 BFNC 的机制。
Benign familiar neonatal convulsion (BFNC) is a common idiopathic epilepsy with autosomal dominant inheritance. Recently, two novel voltage-dependent potassium channel genes, KCNQ2 and KCNQ3, were identified by positional cloning as being responsible for BFNG. Heterotetramers of the products of these genes form M-channels and regulate the threshold of electrical excitability of neurons. We disrupted the mouse KCNQ2 gene via gene targeting to study the relationship between KCNQ2 and epilepsy. Homozygous pups (KCNQ2 -/-) died within a few hours after birth owing to pulmonary atelectasis that was not due to the status of epileptic seizures, although their development was morphologically normal. Heterozygous mice had decreased expression of KCNQ2 and showed hypersensitivity to pentylenetetrazole, an inducer of seizure. These data indicate that the decreased expression of KCNQ2 might cause a hyperexcitability of the CNS, which accounts for the mechanism of BFNC.