Behavior in Drosophila: Analysis and Control
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Summary. Biomedical research increasingly exploits zebrafish ( Danio rerio ) for genetic disease modeling and medical genetic research with the main goals of deciphering and understanding disease processes, and identifying new molecular markers and therapeutic targets. Zebrafish has emerged as a high-throughput and low-cost model organism based on the advantages that include the availability and ease of generating mutations in homologous disease-causing genes, the ability of noninvasive imaging for the analysis of phenotypes of different organs in an intact animal, and the suitability of zebrafish larvae for large-scale chemical screens. Identification of causative genes in human diseases and their functional characterization is enabled by forward and reverse genetic manipulation tools including CRISPR/Cas9-based genome editing. Here we review the use of the zebrafish for biomedical research, with a focus on tumors, cardiovascular diseases and myopathies.
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Abstract Zebrafish is becoming a more and more popular model organism to study human genetic disease. Recent advances in genome editing, including but not limited to the CRISPR/cas technology, have made zebrafish model one of the fastest, cheapest and easiest model to generate mutations similar to the ones identified in human genetic disorders. Based on its size, zebrafish mutant embryos are also a perfect model to be used in chemical preclinical screens to identify novel molecules that are able to compensate for the partial or total inactivation of a gene. Progress in human genome sequencing has recently identified several novel alleles linked to genetic disorders that can now be tested for the identification of novel therapeutics in a zebrafish mutant modelled to phenocopy the human mutation. Key Concepts Zebrafish is a remarkable model to study human genetic diseases The zebrafish genetic tool box has a novel reliable tool: the CRISPR/cas9 technology for reverse genetics Zebrafish as a model for drug discovery Development of zebrafish as a now tool for cure in personalised/precision medicine
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In Darwin’s and Mendel’s times, researchers investigated a wealth of organisms, chosen to solve particular problems for which they seemed especially well suited. Later, a focus on a few organisms, which are accessible to systematic genetic investigations, resulted in larger repertoires of methods and applications in these few species. Genetic animal model organisms with large research communities are the nematode Caenorhabditis elegans , the fly Drosophila melanogaster , the zebrafish Danio rerio, and the mouse Mus musculus. Due to their specific strengths, these model organisms have their strongest impacts in rather different areas of biology. C. elegans is unbeatable in the analysis of cell-to-cell contacts by saturation mutagenesis, as worms can be grown very fast in very high numbers. In Drosophila , a rich pattern is generated in the embryo as well as in adults that is used to unravel the underlying mechanisms of morphogenesis. The transparent larvae of zebrafish are uniquely suited to study organ development in a vertebrate, and the superb versatility of reverse genetics in the mouse made it the model organism to study human physiology and diseases. The combination of these models allows the in-depth genetic analysis of many fundamental biological processes using a plethora of different methods, finally providing many specific approaches to combat human diseases. The plant model Arabidopsis thaliana provides an understanding of many aspects of plant biology that might ultimately be useful for breeding crops.
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