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      Zebrafish and Medaka: new model organisms for modern biomedical research

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          Abstract

          Although they are primitive vertebrates, zebrafish ( Danio rerio) and medaka ( Oryzias latipes) have surpassed other animals as the most used model organisms based on their many advantages. Studies on gene expression patterns, regulatory cis-elements identification, and gene functions can be facilitated by using zebrafish embryos via a number of techniques, including transgenesis, in vivo transient assay, overexpression by injection of mRNAs, knockdown by injection of morpholino oligonucleotides, knockout and gene editing by CRISPR/Cas9 system and mutagenesis. In addition, transgenic lines of model fish harboring a tissue-specific reporter have become a powerful tool for the study of biological sciences, since it is possible to visualize the dynamic expression of a specific gene in the transparent embryos. In particular, some transgenic fish lines and mutants display defective phenotypes similar to those of human diseases. Therefore, a wide variety of fish model not only sheds light on the molecular mechanisms underlying disease pathogenesis in vivo but also provides a living platform for high-throughput screening of drug candidates. Interestingly, transgenic model fish lines can also be applied as biosensors to detect environmental pollutants, and even as pet fish to display beautiful fluorescent colors. Therefore, transgenic model fish possess a broad spectrum of applications in modern biomedical research, as exampled in the following review.

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          Most cited references109

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          Efficient In Vivo Genome Editing Using RNA-Guided Nucleases

          Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems have evolved in bacteria and archaea as a defense mechanism to silence foreign nucleic acids of viruses and plasmids. Recent work has shown that bacterial type II CRISPR systems can be adapted to create guide RNAs (gRNAs) capable of directing site-specific DNA cleavage by the Cas9 nuclease in vitro. Here we show that this system can function in vivo to induce targeted genetic modifications in zebrafish embryos with efficiencies comparable to those obtained using ZFNs and TALENs for the same genes. RNA-guided nucleases robustly enabled genome editing at 9 of 11 different sites tested, including two for which TALENs previously failed to induce alterations. These results demonstrate that programmable CRISPR/Cas systems provide a simple, rapid, and highly scalable method for altering genes in vivo, opening the door to using RNA-guided nucleases for genome editing in a wide range of organisms.
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            Gene silencing by microRNAs: contributions of translational repression and mRNA decay.

            Despite their widespread roles as regulators of gene expression, important questions remain about target regulation by microRNAs. Animal microRNAs were originally thought to repress target translation, with little or no influence on mRNA abundance, whereas the reverse was thought to be true in plants. Now, however, it is clear that microRNAs can induce mRNA degradation in animals and, conversely, translational repression in plants. Recent studies have made important advances in elucidating the relative contributions of these two different modes of target regulation by microRNAs. They have also shed light on the specific mechanisms of target silencing, which, although it differs fundamentally between plants and animals, shares some common features between the two kingdoms.
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              microRNA target predictions in animals.

              In recent years, microRNAs (miRNAs) have emerged as a major class of regulatory genes, present in most metazoans and important for a diverse range of biological functions. Because experimental identification of miRNA targets is difficult, there has been an explosion of computational target predictions. Although the initial round of predictions resulted in very diverse results, subsequent computational and experimental analyses suggested that at least a certain class of conserved miRNA targets can be confidently predicted and that this class of targets is large, covering, for example, at least 30% of all human genes when considering about 60 conserved vertebrate miRNA gene families. Most recent approaches have also shown that there are correlations between domains of miRNA expression and mRNA levels of their targets. Our understanding of miRNA function is still extremely limited, but it may be that by integrating mRNA and miRNA sequence and expression data with other comparative genomic data, we will be able to gain global and yet specific insights into the function and evolution of a broad layer of post-transcriptional control.
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                Author and article information

                Contributors
                +886-2-326360303 Ext 1724 , hjtsai@ntu.edu.tw , hjtsai@mmc.edu.tw
                Journal
                J Biomed Sci
                J. Biomed. Sci
                Journal of Biomedical Science
                BioMed Central (London )
                1021-7770
                1423-0127
                28 January 2016
                28 January 2016
                2016
                : 23
                : 19
                Affiliations
                Graduate Institute of Biomedical Sciences, Mackay Medical College, No.46, Section 3, Zhongzheng Rd., Sanzhi Dist., New Taipei City, 252 Taiwan
                Article
                236
                10.1186/s12929-016-0236-5
                4730764
                26753721
                80f03ee7-52d7-43ef-ab1e-e4a529124482
                © Lin et al. 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 1 November 2015
                : 20 January 2016
                Funding
                Funded by: Ministry of Science and Technology, R. O. C.
                Award ID: 104-2321-B-715 -001-MY3
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2016

                Molecular medicine
                disease model organism,developmental biology,gene regulation,in vivo expression,transgenic fish

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