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Chemical discovery and global gene expression analysis in zebrafish

Abstract

The zebrafish (Danio rerio) provides an excellent model for studying vertebrate development and human disease because of its ex utero, optically transparent embryogenesis and amenability to in vivo manipulation. The rapid embryonic developmental cycle, large clutch sizes and ease of maintenance at large numbers also add to the appeal of this species. Considerable genomic data has recently become publicly available that is aiding the construction of zebrafish microarrays, thus permitting global gene expression analysis. The zebrafish is also suitable for chemical genomics, in part as a result of the permeability of its embryos to small molecules and consequent avoidance of external confounding maternal effects. Finally, there is increasing characterization and analysis of zebrafish models of human disease. Thus, the zebrafish offers a high-quality, high-throughput bioassay tool for determining the biological effect of small molecules as well as for dissecting biological pathways.

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Figure 1: Uses of the zebrafish and the assay tools currently available.
Figure 2: Small-molecule inhibition of apoptosis gene orthologs in zebrafish.
Figure 3: The utility of zebrafish in the drug design and development process.

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Acknowledgements

We acknowledge funding support of the University of Auckland Vice Chancellor's Development Fund, University of Auckland Research Committee, Lottery Grants Board of New Zealand and the Maurice and Phyllis Paykel Trust. We thank Vivienne Ward for assistance in graphics production.

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Correspondence to Donald R Love.

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Pichler, F., Laurenson, S., Williams, L. et al. Chemical discovery and global gene expression analysis in zebrafish. Nat Biotechnol 21, 879–883 (2003). https://doi.org/10.1038/nbt852

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