Rennekamp Andrew J, Peterson Randall T
Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA; Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA; Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA.
Cardiovascular Research Center and Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA; Department of Systems Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA; Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA.
Curr Opin Chem Biol. 2015 Feb;24:58-70. doi: 10.1016/j.cbpa.2014.10.025. Epub 2014 Nov 15.
In 2000, the first chemical screen using living zebrafish in a multi-well plate was reported. Since then, more than 60 additional screens have been published describing whole-organism drug and pathway discovery projects in zebrafish. To investigate the scope of the work reported in the last 14 years and to identify trends in the field, we analyzed the discovery strategies of 64 primary research articles from the literature. We found that zebrafish screens have expanded beyond the use of developmental phenotypes to include behavioral, cardiac, metabolic, proliferative and regenerative endpoints. Additionally, many creative strategies have been used to uncover the mechanisms of action of new small molecules including chemical phenocopy, genetic phenocopy, mutant rescue, and spatial localization strategies.
2000年,有报道称首次在多孔板中使用活斑马鱼进行化学筛选。从那时起,又发表了60多篇关于斑马鱼全生物体药物和通路发现项目的筛选报告。为了研究过去14年报道的工作范围并确定该领域的趋势,我们分析了文献中64篇主要研究文章的发现策略。我们发现,斑马鱼筛选已从利用发育表型扩展到包括行为、心脏、代谢、增殖和再生终点。此外,还采用了许多创新策略来揭示新小分子的作用机制,包括化学拟表型、遗传拟表型、突变体拯救和空间定位策略。