Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
Expert Opin Drug Discov. 2023 Jun;18(6):629-641. doi: 10.1080/17460441.2023.2211802. Epub 2023 May 15.
Zebrafish larvae are one of the few vertebrates amenable to large-scale drug discovery screens. Larval swimming behavior is often used as an outcome variable and many fields of study have developed assays for evaluating swimming performance. An unintended consequence of this wide interest is that details related to assay methodology and interpretation become scattered across the literature. The aim of this review is to consolidate this information, particularly as it relates to high-throughput approaches.
The authors describe larval swimming behaviors as this forms the basis for understanding their experimentally evoked swimming or spontaneous activity. Next, they detail how swimming activity can serve as an outcome variable, particularly in the multi-well formats used in large-scale screening studies. They also highlight biological and technical factors that can impact the sensitivity and variability of these measurements.
Careful attention to animal husbandry, experimental design, data acquisition, and interpretation of results can improve screen outcomes by maximizing swimming activity while minimizing intra- and inter-larval variability. The development of more sensitive, quantitative methods of assessing swimming performance that can be incorporated into high-throughput workflows will be important in order to take full advantage of the zebrafish model.
斑马鱼幼鱼是少数几种适合大规模药物发现筛选的脊椎动物之一。幼鱼的游泳行为通常用作结果变量，许多研究领域已经开发出用于评估游泳性能的测定方法。这种广泛关注的一个意外后果是，与测定方法学和解释相关的细节在文献中分散开来。本综述的目的是整合这些信息，特别是与高通量方法相关的信息。
作者描述了幼鱼的游泳行为，因为这是理解其实验诱发的游泳或自发活动的基础。接下来，他们详细介绍了游泳活动如何作为一个结果变量，特别是在用于大规模筛选研究的多孔板格式中。他们还强调了可能影响这些测量的灵敏度和可变性的生物学和技术因素。
通过最大限度地提高游泳活动，同时最小化个体内和个体间的变异性，仔细注意动物饲养、实验设计、数据采集和结果解释，可以改善筛选结果。开发更敏感、定量的游泳性能评估方法，并将其纳入高通量工作流程，对于充分利用斑马鱼模型将是重要的。
