Griffin A, Krasniak C, Baraban S C
Epilepsy Research Laboratory, University of California, San Francisco, CA, United States.
Epilepsy Research Laboratory, University of California, San Francisco, CA, United States.
Prog Brain Res. 2016;226:195-207. doi: 10.1016/bs.pbr.2016.03.012. Epub 2016 Apr 20.
With an increase in the number of disease causing genetic mutations identified from epilepsy cohorts, zebrafish are proving to be an attractive vertebrate model for functional analysis of these allele variants. Not only do zebrafish have conserved gene functions, but larvae harboring mutations in identified human epileptic genes show spontaneous seizure activity and mimic the convulsive behavioral movements observed in humans. With zebrafish being compatible with medium to high-throughput screening, they are also proving to be a unique and powerful system for early preclinical drug screening, including novel target identification, pharmacology, and toxicology. Additionally, with recent advances in genomic engineering technologies, it is now possible to study the precise pathophysiology of patient-specific gene mutations in zebrafish. The following sections highlight how the unique attributes of zebrafish, in combination with genetic modifications, are continuing to transform our understanding of epilepsy and help identify personalized therapeutics for specific patient cohorts.
随着从癫痫队列中鉴定出的致病基因突变数量的增加，斑马鱼正被证明是用于这些等位基因变体功能分析的有吸引力的脊椎动物模型。斑马鱼不仅具有保守的基因功能，而且在已鉴定的人类癫痫基因中携带突变的幼虫会表现出自发性癫痫活动，并模仿人类中观察到的惊厥行为动作。由于斑马鱼适用于中高通量筛选，它们也被证明是早期临床前药物筛选的独特而强大的系统，包括新靶点鉴定、药理学和毒理学。此外，随着基因组工程技术的最新进展，现在有可能在斑马鱼中研究患者特异性基因突变的精确病理生理学。以下各节重点介绍斑马鱼的独特特性与基因修饰相结合如何继续改变我们对癫痫的理解，并有助于为特定患者群体确定个性化治疗方法。
