The zebrafish (Danio rerio) is a tropical fresh water fish originating from southeast Asia. Zebrafish are not only a favorite of many home aquaria, but figure prominently as a vertebrate model for developmental, genetic, and biomedical research. Zebrafish have a short generation time of about three months. Adult zebrafish are small (approximately 2-3 cm long) and thus can be economically maintained with relative ease in the laboratory. Zebrafish eggs are fertilized externally and the resulting transparent embryos develop rapidly. One day after fertilization, rudimentary organs such as the brain, eyes, ears, and heart can be observed in the embryos. A pair of zebrafish is able to produce several hundred embryos weekly. These attributes make zebrafish an ideal model for large-scale phenotype-driven forward mutagenesis screens.

In recent years, many aspects of zebrafish early development, including embryonic patterning, nervous system development, and cell fate specification and lineage determination, have been elucidated. Several thousands of chemical and insertional mutants with defects in almost every aspect of the development have been found in large-scale mutagenesis screens. To facilitate isolation of these mutants, the zebrafish community has generated several genetic maps and over 1,000, 000 ESTs (Expressed Sequence Tags). In particular, the Sanger Center has nearly completed sequencing the whole genome. Additionally, we also are able to overexpress genes of particular interest and use Morphorlino oligos to "knock them down" in living zebrafish embryos, selectively inactivate genes by resequencing and TILLING (Targeting Induced Local Lesions IN Genomes).

Through comparative approaches, the zebrafish and human genomes are shown to share extensive conserved syntenic fragments and many zebrafish genes and their human homologs share structural and functional similarities. Several zebrafish models have been established for human diseases. Thus, studying the zebrafish would help understand human embryonic development, physiology and behaviors, and fight against various human diseases.

 

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