Fish Pharming: Identifying Gene Function and Therapeutic Targets Using Pharmacologic Treatment of Zebrafish Embryos

M.      Kamkar; M.   A.   Steggles; C.   C.   Martin

doi:10.2174/157016006776286846

Abstract

One of the remaining challenges for the post-genomic era researcher is the systematic assignment of gene function to a sequenced genome. The zebrafish is an effective model organism for conducting comparative analyses of the human genome. The ability to obtain large numbers of zebrafish embryos, grow them in a 96-well dish, and then expose them to molecules dissolved in their water, underline the valuable characteristics of this organism that is currently being explored by academic and private researchers. This high throughput strategy is being applied to evaluate the specificity and the cellular toxicity of environmental toxins and new drug therapies. Similarly, small molecules, metabolic inhibitors, enzyme antagonist and agonist or receptor/ligand substitutes have been used to enhance our understanding of developmental and physiological pathways and gene cascades. These studies also introduce valuable systems that can be employed to investigate the pathologies that can occur when these pathways are disrupted. Pharmacologics act primarily at the post-translational level, the proteome. These results are further supported by comparative genomic studies using the numerous zebrafish mutants that are available or by targeted gene knockdowns using antisense morpholino oligonucleotides. The conservation of genetic mechanisms across a wide range of phyla ensures that the results obtained from fish can be directly transferred to humans.

Keywords: genetic approaches, mutations, Hydroxymethylglutaryl coenzyme A reductase, geranylgeranyl transferase 1(GTT1), apoptosis

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