Rennekamp Andrew J
Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Methods Mol Biol. 2018;1787:147-159. doi: 10.1007/978-1-4939-7847-2_11.
High-throughput, whole-organism phenotypic drug screening is made possible using live zebrafish larvae. Many human drugs have now been shown to affect zebrafish larvae in similar ways, through homologous molecular mechanisms. At this stage in life, zebrafish are small enough to fit in multi-well, microliter plates, yet developed enough to exhibit complex phenotypes, such as hunting behaviors and avoidance of predators. Importantly, zebrafish larvae can be easily dosed via automated pipetting of chemical compounds directly into their liquid medium, without injection. Only microgram amounts of small molecules are required, making animal husbandry and dosing regimens cost effective. This chapter describes how the stereotyped zebrafish larval responses to darkness and strobe light-which cause hyperactivity and freezing behavior, respectively-can be used to efficiently screen small molecules for brain and behavior-modulating activity.
利用活的斑马鱼幼体可实现高通量、全生物体表型药物筛选。现在已证明，许多人类药物通过同源分子机制以类似方式影响斑马鱼幼体。在生命的这个阶段，斑马鱼体型小到足以放入多孔微升板中，但又发育到足以表现出复杂的表型，如捕食行为和躲避捕食者。重要的是，斑马鱼幼体可以通过将化合物直接自动移液到其液体培养基中轻松给药，无需注射。只需要微克量的小分子，这使得动物饲养和给药方案具有成本效益。本章描述了如何利用斑马鱼幼体对黑暗和频闪灯光的刻板反应（分别导致多动和僵住行为）来有效筛选具有脑和行为调节活性的小分子。
