斑马鱼中的小分子筛选

Small molecule screening in the zebrafish.

作者信息

Murphey R D, Zon L I

机构信息

Stem Cell Program and Division of Hematology and Oncology, Children's Hospital, Dana-Farber Cancer Institute, Howard Hughes Medical Institute and Harvard Medical School, 1 Blackfan Circle, Boston, MA 02115, USA.

出版信息

Methods. 2006 Jul;39(3):255-61. doi: 10.1016/j.ymeth.2005.09.019.

DOI:10.1016/j.ymeth.2005.09.019

PMID:16877005

Abstract

The zebrafish is an ideal organism for small molecule studies. The ability to use the whole organism allows complex in vivo phenotypes to be assayed and combines animal testing with screening. Embryos are easily treatable by waterborne exposure. The small size and abundance of embryos make zebrafish suitable for screening in a high-throughput manner in 96- or 48-well plates. Zebrafish embryos have successfully been used in chemical genetic screens to elucidate biological pathways and find chemical suppressors. Small molecules discovered by screening zebrafish disease models may also be useful as lead compounds for drug development as there appears to be a high level of conservation of drug activity between mammals and zebrafish. Here we provide the technical aspects of treating embryos with small molecules and performing chemical screens with zebrafish.

摘要

斑马鱼是小分子研究的理想生物体。使用整个生物体的能力使得能够检测复杂的体内表型，并将动物试验与筛选相结合。胚胎通过水体暴露易于处理。胚胎的小尺寸和丰富数量使斑马鱼适合于在96孔或48孔板中以高通量方式进行筛选。斑马鱼胚胎已成功用于化学遗传筛选，以阐明生物学途径并寻找化学抑制剂。通过筛选斑马鱼疾病模型发现的小分子也可能用作药物开发的先导化合物，因为哺乳动物和斑马鱼之间的药物活性似乎高度保守。在此，我们提供用小分子处理胚胎以及对斑马鱼进行化学筛选的技术要点。