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

通过对中枢神经系统离子通道编码基因突变的基因分析，我们有以下发现：所使用的标本保存在银行中，保存着从各种癫痫综合征患者身上获得的DNA样本。在广泛性癫痫伴热性发作+ (GEFS+)患者中，在编码Na+通道a1亚基的基因SCN1A中发现了两个新的突变。此外，我们发现编码Na+通道a2亚基的基因SCN2A与常染色体显性癫痫伴发热性癫痫发作相关。突变导致通道功能的缓慢失活，从而导致通道的超不可模仿性。利用上述结果，我们已经产生了转基因动物（大鼠），其中含有在人类癫痫中发现的相同突变。其中一只携带CHRNA4突变的动物表现出抽搐。目前正在研究这些动物的药理学和电生理特性。

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.