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Zebrafish as a model system for mitochondrial biology and diseases: a review.
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Transl Res 2013 Sep;
Authors: S L Steele, S V Prykhozhij, Jason N Berman
Department of Pediatrics, Dalhousie University, IWK Health Centre, Halifax, Nova Scotia, Canada.
Animal models for studying human disease are essential to the continuing evolution of medicine. Rodent models are attractive for the obvious similarities in development and genetic makeup compared with humans, but have cost and technical limitations. The zebrafish (Danio rerio) represents an excellent alternative vertebrate model of human disease because of its high conservation of genetic information and physiological processes, inexpensive maintenance, and optical clarity facilitating direct observation. This review highlights recent advances in understanding genetic disease states associated with the dynamic organelle, the mitochondrion, using zebrafish. Mitochondrial diseases that have been replicated in the zebrafish include those affecting the nervous and cardiovascular systems, as well as red blood cell function. There are a large number of studies involving genes associated with Parkinson's disease, as well as many of the genes associated with heme synthesis and anemia. Gene silencing techniques, including morpholino knockdown and TAL-effector endonucleases have been exploited to demonstrate how loss of function can induce human diseaselike states in zebrafish. Moreover, modeling mitochondrial diseases has been facilitated greatly by the creation of transgenic fish with fluorescently labeled mitochondria for in†vivo visualization of these structures. In addition, behavioral assays have been developed to examine changes in motor activity and sensory responses, particularly in larval stages. Zebrafish are poised to advance our understanding of the pathogenesis of human mitochondrial diseases beyond the current state of knowledge and provide a key tool in the development of novel therapeutic approaches to treat these conditions.
PMID: 24055494 [PubMed - as supplied by publisher]