TY -的T1 -描述小说敲入小鼠模型的KCNT1癫痫性脑病(P2.273) JF -神经学乔-神经学六世- 90 - 15补充SP - P2.273盟Lisseth Burbano AU -旋律李盟尼古拉Jancovski首页 AU -理查兹凯盟Elena Gazina盟Snezana Maljevic AU -克里斯托弗·里德盟史蒂文Petrou Y1 - 2018/04/10 UR - //www.ez-admanager.com/content/90/15_Supplement/P2.273.abstract N2 -目的:描述一个敲入小鼠模型的KCNT1癫痫脑病。背景:癫痫发作的初级阶段的迁移焦(EIMFS)是一种严重的儿童癫痫的特征是发病早期,难治性癫痫,全球发育迟缓和认知障碍。新创KCTN1钠激活钾通道基因的突变被发现在50%的病人。p。Pro924Leu突变被发现与EIMFS 2例,异源表达系统在体外研究显示函数的一个重要获得突变的影响,导致大量钾电流比野生型(WT)通道。设计/方法C57BL / 6小鼠转基因的p。P924L变异使用CRISPR / Cas系统生成。视频皮层脑电图(视频/ ECoG)分析,热,chemoconvulsant (Pentylenetetrazole和洛沙平)测试进行评估癫痫易感性。运动活动和筑巢行为进行评估筛选运动功能障碍和认知障碍。结果:杂合的Kcnt1 (L / +)小鼠显示没有增加易感性热或化学诱导癫痫发作而Kcnt1 WT(+ / +)老鼠。在视频/ ECoG没有发现差异,嵌套和运动活动Kcnt1 (L / +)和Kcnt1 WT(+ / +)老鼠。相比之下,纯合子Kcnt1 (L / L)老鼠是规模较小,表现出自发的强直性阵挛性的癫痫,受损的筑巢行为和缩短寿命。 ECoG analysis revealed ictal discharges that coincide with convulsive seizures as well as interictal spikes in these mice.Conclusions: Kcnt1(L/L) mice provide a model of epileptic encephalopathy that will be valuable for studying the in vivo effects of gain of function KCNT1 mutations and the response to targeted therapeutic interventions.Disclosure: Dr. Burbano has nothing to disclose. Dr. Lin has nothing to disclose. Dr. Jancovsky has nothing to disclose. Dr. Richards has nothing to disclose. Dr. Gazina has nothing to disclose. Dr. Maljevic has nothing to disclose. Dr. Reid has nothing to disclose. Dr. Petrou has received compensation for serving on the Board of Directors of Pairnomix, Praxis Precision Medicine, RogCon. Dr. Petrou holds stock and/or stock options in Pairnomix, Praxis Precision Medicine, RogCon, which sponsored research in which Dr. Petrou was involved as an investigator. Dr. Petrou has received research support from Praxis Precision Medicine, RogCon. ER -