IDEXX BioAnalytics, Columbia, MO, USA.
Boston Children's Hospital, Boston, MA, USA.
Lab Anim (NY). 2021 Jan;50(1):19-25. doi: 10.1038/s41684-020-00683-x. Epub 2020 Dec 2.
Poorly controlled background genetics in animal models contributes to the lack of reproducibility that is increasingly recognized in biomedical research. The laboratory zebrafish, Danio rerio, has been an important model organism for decades in many research areas, yet inbred strains and traditionally managed outbred stocks are not available for this species. Sometimes incorrectly referred to as 'inbred strains' or 'strains', zebrafish wild-type lines possess background genetics that are often not well characterized, and breeding practices for these lines have not been consistent over time or among institutions. In this Perspective, we trace key milestones in the history of one of the most widely used genetic backgrounds, the AB line, to illustrate the dynamic complexity within an example background that is largely invisible when reading the scientific literature. Failure to adequately control for genetic background compromises the validity of experimental outcomes. We therefore propose that authors provide as much specific detail about the origin and genetic makeup of zebrafish lines as is reasonable and possible, and that the terms used to describe background genetics be applied in a way that is consistent with other fish and mammalian model organisms. We strongly encourage the adoption of genetic monitoring for the characterization of existing zebrafish lines, to help detect genetic contamination in breeding colonies and to verify the level of genetic heterogeneity in breeding colonies over time. Careful attention to background genetics will improve transparency and reproducibility, therefore improving the utility of the zebrafish as a model organism.
动物模型中控制不佳的背景遗传学导致了生物医学研究中越来越多的可重复性问题。实验室斑马鱼（Danio rerio）作为一种重要的模式生物，在许多研究领域已经使用了几十年，但该物种缺乏近交系和传统管理的远交系。由于有时被错误地称为“近交系”或“品系”，野生型斑马鱼系具有背景遗传学特征，这些特征通常没有很好地描述，并且这些系的繁殖实践在时间上或机构之间并不一致。在本文中，我们追溯了最广泛使用的遗传背景之一 AB 系的历史上的关键里程碑，以说明在阅读科学文献时通常看不到的一个背景中的动态复杂性。未能充分控制遗传背景会影响实验结果的有效性。因此，我们建议作者尽可能详细地提供有关斑马鱼系的起源和遗传组成的具体信息，并以与其他鱼类和哺乳动物模式生物一致的方式应用描述背景遗传学的术语。我们强烈鼓励采用遗传监测来描述现有的斑马鱼系，以帮助检测繁殖群体中的遗传污染，并验证繁殖群体中遗传异质性的水平随时间的变化。仔细注意背景遗传学将提高透明度和可重复性，从而提高斑马鱼作为模型生物的实用性。
