Barclay J, Rees M
Department of Paediatrics, The Rayne Institute, University College London Medical School, England, UK.
Epilepsia. 1999;40 Suppl 3:17-22. doi: 10.1111/j.1528-1157.1999.tb00894.x.
The mouse is a well-established model for human genetic disorders. An increasing number of single-gene human diseases are being elucidated through the use of mouse models. Recently genes for three of the six well-characterised single locus models for human spike-wave epilepsy have been isolated and published. The tottering mouse has been shown to be due to mutations in the gene encoding the high voltage-activated alpha1A calcium channel subunit. The lethargic mouse has been shown to be due to mutations in the gene encoding another calcium channel subunit, beta4. The slow-wave epilepsy mouse phenotype is the result of loss of function of the ubiquitous sodium hydrogen exchanger NHEI. These genes and the pathways they are involved in are now candidates for human spike-wave epilepsy. The six mouse models and those genes underlying the spike-wave phenotype are discussed in conjunction with how these mutations were discovered and how they may give rise to the seizure phenotypes. Several nonepilepsy human neurologic disorders have been shown to be allelic with the tottering mouse. The question this raises as to the validity of these models for human spike-wave epilepsy is considered. Finally, the effect these discoveries will have on the understanding and treatment of human spike-wave epilepsy are discussed.
小鼠是研究人类遗传疾病的成熟模型。通过使用小鼠模型，越来越多的单基因人类疾病得以阐明。最近，人类棘波癫痫的六个特征明确的单基因座模型中的三个基因已被分离并发表。蹒跚小鼠已被证明是由于编码高电压激活的α1A钙通道亚基的基因突变所致。嗜睡小鼠已被证明是由于编码另一种钙通道亚基β4的基因突变所致。慢波癫痫小鼠的表型是普遍存在的钠氢交换体NHEI功能丧失的结果。这些基因及其所涉及的途径现在是人类棘波癫痫的候选因素。本文结合这些突变是如何被发现的以及它们如何导致癫痫发作表型，讨论了这六个小鼠模型以及棘波表型背后的那些基因。已证明几种非癫痫性人类神经疾病与蹒跚小鼠等位基因相同。本文考虑了这对这些模型用于人类棘波癫痫的有效性所提出的问题。最后，讨论了这些发现将对人类棘波癫痫的理解和治疗产生的影响。
