Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, San Francisco, 513 Parnassus Ave., San Francisco, CA 94143, USA.
Dis Model Mech. 2010 Mar-Apr;3(3-4):144-8. doi: 10.1242/dmm.002139.
Despite a long tradition of using rats and mice to model epilepsy, several aspects of rodent biology limit their use in large-scale genetic and therapeutic drug screening programs. Neuroscientists interested in vertebrate development and diseases have recently turned to zebrafish (Danio rerio) to overcome these limitations. Zebrafish can be studied at all stages of development and several methods are available for the manipulation of genes in zebrafish. In addition, developing zebrafish larvae can efficiently equilibrate drugs placed in the bathing medium. Taking advantage of these features and adapting electrophysiological recording methods to an agar-immobilized zebrafish preparation, we describe here our efforts to model seizure disorders in zebrafish. We also describe the initial results of a large-scale mutagenesis screen to identify gene mutation(s) that confer seizure resistance. Although the adaptation of zebrafish to epilepsy research is in its early stages, these studies highlight the rapid progress that can be made using this simple vertebrate species.
尽管长期以来一直使用大鼠和小鼠来模拟癫痫，但啮齿动物生物学的几个方面限制了它们在大规模遗传和治疗药物筛选计划中的应用。对脊椎动物发育和疾病感兴趣的神经科学家最近转向斑马鱼（Danio rerio）来克服这些限制。斑马鱼可以在发育的所有阶段进行研究，并且有几种方法可用于操纵斑马鱼中的基因。此外，发育中的斑马鱼幼虫可以有效地平衡放置在沐浴介质中的药物。利用这些特性并将电生理记录方法适用于琼脂固定的斑马鱼制剂，我们在这里描述了我们在斑马鱼中模拟癫痫发作障碍的努力。我们还描述了大规模诱变筛选以鉴定赋予抗癫痫作用的基因突变的初步结果。尽管斑马鱼向癫痫研究的适应还处于早期阶段，但这些研究突出了使用这种简单的脊椎动物物种可以取得的快速进展。
