The Advantages of the Zebrafish Model System
Zebrafish offer a powerful combination of low cost, rapid in vivo analysis and complex vertebrate biology. Zebrafish's competitive advantage over other model systems is optical clarity in a vertebrate embryo amenable to large-scale screening, including genetic and small molecule drug screens. Zebrafish are closer to humans evolutionarily than yeast or insects or worms and experiments are faster and less costly than those using mice.
Transparent Embryogenesis
Zebrafish embryos are transparent vertebrates that develop outside the mother's body. The fish change from egg to well-developed embryo within 24 hours and researchers can watch the entire process under a microscope. The fish embryos develop organs that are similar to those in humans, such as central nervous system, pancreas, and thymus and quickly form blood vessels and beating hearts. It is known that mechanisms of embryonic tissue or organ development are similar or identical to the regeneration process in adults.
Relevance to human disease
Zygogen believes that identifying novel, tissue-specific genes or elucidating the function of "known" genes expressed in the developing zebrafish will shed light on medically relevant processes in humans, such as inflammation, angiogenesis, neuronal growth, bone and muscle formation and insulin regulation. Zebrafish genes demonstrate on average greater than 75% similarity to human genes. The characterization of many mutants from large-scale mutagenesis performed to date has clearly and repeatedly demonstrated that mutations in zebrafish orthologues of human disease genes produce phenotypes similar to human disease states. In addition, there are zebrafish orthologues for human genes that are known to play a role in disease states. Of particular relevance for drug discovery, strong biological conservation between zebrafish and humans is evidenced by drugs tested in Zygogen’s zebrafish assays having the predicted effect and targets that are knocked down have the predicted phenotypes.
Growth of zebrafish as a model organism
There continues to be a steady increase in the number of zebrafish aquaria facilities and laboratories using zebrafish as a model organism. Most major Universities have one or more zebrafish core facilities. The 2004 biennial zebrafish meeting in Madison, WI was highly over-subscribed and featured over 600 presentations. The National Institute of Health (NIH) ranked developmental systems for research and found zebrafish to be third behind humans and mice. NIH's support of academic research in zebrafish has been growing rapidly and scientists are encouraged to apply for more and larger RO1 grants. There have been several Request For Applications programs (RFAs) initiated by NIH specifically targeting zebrafish research in the areas of genomic tool and assay development. Indeed, the NIH is building a $10 million dollar, 5000-squ. Ft. zebrafish aquaria facility to be shared among several NIH researchers. The zebrafish genome sequence is close to completion (Sanger Center and collaborators). The availability of raw zebrafish sequences has increased the facility of isolating genes and manipulating the zebrafish genome. At present there is a publicly available EST database with approximately 355,000 sequences.
ZEBRAFISH AS A MODEL ORGANISM - OVERVIEW