generation of epilepsy model animals harboring the same genetic defects identified in human epilepsy

基于对中枢神经系统离子通道编码基因突变的遗传分析，我们取得了以下发现。所使用的样本在银行中，保存着从各种癫痫综合征患者那里获得的DNA样本。在全身性癫痫伴热性惊厥加(GEFS+)患者中发现了两个新的基因突变，编码Na+通道A1亚单位的SCN1a。此外，我们还发现编码Na+通道α2亚单位的基因SCN2A与常染色体显性遗传性癫痫伴热性惊厥+有关。突变导致通道功能的缓慢失活，从而导致通道的高度不可复制性。利用上述结果，我们产生了转基因动物(大鼠)，它们具有与人类癫痫相同的突变。其中一只携带CHRNA4突变的动物出现了抽搐。目前正在研究这些动物的药理和电生理特性。

We have made the following discoveries based on the genetic analyses searching mutations of genes encoding ion channels expressed in the central nerve system. The specimens used were in the bank holding DNA samples obtained from patients with various epilepsy syndrome. Two novel mutations have been identified in the gene encoding a1 subunit of Na+ channel, SCN1A in patients with generalized epilepsy with febrile seizures plus (GEFS+). Furthermore, we found that the gene encoding a2 subunit of Na+ channel, SCN2A is associated with autosomal dominant epilepsy with febrile seizures plus. The mutation result in slow inactivation in the channel function thereby cause hyper inimitability of the channel. Exploiting the above results, we have generated transgenic animals (rats), which harboring the same mutations identified in human epilepsy. One of such animals, that bears a CHRNA4 mutation showed convulsions. Pharmacological and electrophysiological characteristics of the animals are currently investigated.