Sound-induced seizures in serotonin 5-HT2C receptor mutant mice
Sound-induced seizures in serotonin 5-HT2C receptor mutant mice
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DOI：
10.1038/ng0897-387
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发表时间：
1997-08-01
期刊：
影响因子：
30.8
通讯作者：
Tecott, LH
中科院分区：
文献类型：
--
作者：
Brennan, TJ;Seeley, WW;Tecott, LH
癫痫是癫痫发作疾病的异质性集合，终生预期风险率为2-4%（1）。证据表明，遗传因素对癫痫发作易感性有显著影响（2，3）。遗传性癫痫倾向的啮齿动物品系已被频繁地用于检查遗传因素对癫痫发作易感性的影响。其中研究最广泛的是对声音诱发的惊厥（听源性癫痫发作，或AGS）敏感的菌株。对ACS现象的早期观察是在Ivan Pavlov博士的实验室中进行的;在小鼠的食欲调节实验过程中，用于发出食物呈现信号的响亮铃声意外地在一些动物中引起癫痫发作（4）。1947年，DBA/2（D2）小鼠被发现对安装在铁盆中的门铃刺激的AGS表现出遗传易感性（5）。自这一发现以来，AGS一直是行为遗传学中研究最深入的表型之一（6，7）。虽然几个遗传位点赋予AGSs的易感性，但相应的基因尚未被克隆。我们报告说，空突变小鼠缺乏5-羟色胺5-HT 2C受体是非常容易受到AGSs。易感性在两到三个月大之间开始，成年动物完全外显。ACS诱导的即刻早期基因表达表明，AGSs是听觉回路中的皮层下现象。这AGS综合征是第一个已知的遗传缺陷产生的，它提供了一个强大的模型，检查癫痫的胆碱能机制。
The epilepsies are a heterogeneous collection of seizure disorders with a lifetime expectancy risk rate of 2-4%(1). A convergence of evidence indicates that heritable factors contribute significantly to seizure susceptibility(2,3). Genetically epilepsy-prone rodent strains have been frequently used to examine the effect of genetic factors on seizure susceptibility. The most extensively studied of these have been strains that are susceptible to sound-induced convulsions (audiogenic seizures, or AGSs). Early observations of the ACS phenomenon were made in the laboratory of Dr. Ivan Pavlov; in the course of appetite-conditioning experiments in mice, the loud bell used to signal food presentation unexpectedly produced seizures in some animals(4). In 1947, DBA/2 (D2) mice were found to exhibit a genetic susceptibility to AGSs stimulated by a doorbell mounted in an iron tub(5). Since this discovery, AGSs have been among the most intensively studied phenotypes in behavioural genetics(6,7). Although several genetic loci confer susceptibility to AGSs, the corresponding genes have not been cloned. We report that null mutant mice lacking serotonin 5-HT2C receptors are extremely susceptible to AGSs. The onset of susceptibility is between two and three months of age, with complete penetrance in adult animals. ACS-induced immediate early gene expression indicates that AGSs are subcortical phenomena in auditory circuits. This AGS syndrome is the first produced by a known genetic defect; it provides a robust model for the examination of serotoninergic mechanisms in epilepsy.