Bedell Victoria, Buglo Elena, Marcato Daniel, Pylatiuk Christian, Mikut Ralf, Stegmaier Johannes, Scudder Will, Wray Maxwell, Züchner Stephan, Strähle Uwe, Peravali Ravindra, Dallman Julia E
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States.
John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, United States; Dr. John T. MacDonald Foundation, University of Miami, Miami, FL, United States; University of Miami, Coral Gables, FL, United States.
Methods Enzymol. 2018;602:189-209. doi: 10.1016/bs.mie.2018.02.004. Epub 2018 Mar 15.
General anesthetics are small molecules that interact with and effect the function of many different proteins to promote loss of consciousness, amnesia, and sometimes, analgesia. Owing to the complexity of this state transition and the transient nature of these drug/protein interactions, anesthetics can be difficult to study. The zebrafish is an emerging model for the discovery of both new genes required for the response to and side effects of anesthesia. Here we discuss the tools available to manipulate the zebrafish genome, including both genetic screens and genome engineering approaches. Additionally, there are various robust behavior assays available to study anesthetic and other drug responses. These assays are available for single-gene study or high throughput for genetic or drug discovery. Finally, we present a case study of using propofol as an anesthetic in the zebrafish. These techniques and protocols make the zebrafish a powerful model to study anesthetic mechanisms and drug discovery.
全身麻醉药是小分子，它们与许多不同的蛋白质相互作用并影响其功能，以促进意识丧失、失忆，有时还会产生镇痛作用。由于这种状态转变的复杂性以及这些药物/蛋白质相互作用的短暂性，麻醉药可能难以研究。斑马鱼正成为一种新兴模型，用于发现麻醉反应所需的新基因以及麻醉的副作用。在这里，我们讨论可用于操纵斑马鱼基因组的工具，包括遗传筛选和基因组工程方法。此外，还有各种强大的行为分析方法可用于研究麻醉和其他药物反应。这些分析方法可用于单基因研究或高通量的基因或药物发现。最后，我们展示了一个在斑马鱼中使用丙泊酚作为麻醉剂的案例研究。这些技术和方案使斑马鱼成为研究麻醉机制和药物发现的强大模型。
