Zebrafi sh – an in vivo model for drug screening

The increasing number and diversity of compounds made available by rapid synthesis techniques such as combinatorial chemistry, combined with high throughput or ultra-high throughput in vitro drug screening assays, generate large numbers of preliminary “hits”. However, validating these preliminary hits by mammalian animal models is very slow and costly, resulting in a gap in the drug development process. The zebrafi sh is a vertebrate model organism that can bridge this gap. Zebrafi sh-based assays combine the advantages of higher throughput analysis (compared with mammalian models) and higher relevance to humans (compared with in vitro and invertebrate models). Drug screening assays in diverse formats have been developed using zebrafi sh, including visual assessment of effects on organs in the transparent embryo and quantitative assays using microplates. The microplate-based quantitative assays can be performed in a similar fashion to cell-based assays, and can be used for primary drug screening at high throughput. In this article, we review the recent advances in applying in vivo zebrafi sh assays for testing drug toxicity and drug effects on angiogenesis and apoptosis. The zebrafi sh as a model organism The zebrafi sh (Danio rerio) is a small fresh-water teleost well suited for preclinical drug screening (Figure 1). Zebrafi sh are easy to maintain and breed: large numbers can be housed in a small space, and the generation time (around three months) is relatively short. Mating is not seasonal, and each female can produce 100-200 eggs per mating, DRUG DISCOVERY