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      The golden (Syrian) hamster as a model for the study of reproductive biology: Past, present, and future

      review-article
      1 , 1 , 2 , 3 ,
      Reproductive Medicine and Biology
      John Wiley and Sons Inc.
      embryo, fertilization, hamster, ICSI, spermatozoon

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          Abstract

          Background

          The golden (Syrian) hamster ( Mesocricetus auratus) is a small rodent that belongs to the Cricetidae family. It has several unique features that are advantageous for the study of reproductive and developmental biology, including a consistent estrous cycle (4 days), high responsiveness to conventional superovulation regimens, and the short gestation period (16 days).

          Methods

          Based on the published reports, the development in assisted reproductive technology (ART) in the golden hamsters was summarized.

          Main findings

          The technical ease of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in this species has contributed to our understanding of the basic mechanisms of mammalian fertilization in the last century. However, a strong developmental block in vitro of hamster embryos and unavailability of gene‐modified strains has hampered its broader use in biomedical fields. A recently developed in vivo transfection method has enabled us to generate gene knockout hamsters without any major obstacles. It would be interesting to revisit the genes whose functions could not be identified using mouse models.

          Conclusion

          The authors expect that gene knockout hamsters might be able to substitute for mice—at least in part—for better understanding of gene functions in mammals including humans.

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          Most cited references39

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          Targeted integration in rat and mouse embryos with zinc-finger nucleases.

          Gene targeting is indispensible for reverse genetics and the generation of animal models of disease. The mouse has become the most commonly used animal model system owing to the success of embryonic stem cell-based targeting technology, whereas other mammalian species lack convenient tools for genome modification. Recently, microinjection of engineered zinc-finger nucleases (ZFNs) in embryos was used to generate gene knockouts in the rat and the mouse by introducing nonhomologous end joining (NHEJ)-mediated deletions or insertions at the target site. Here we use ZFN technology in embryos to introduce sequence-specific modifications (knock-ins) by means of homologous recombination in Sprague Dawley and Long-Evans hooded rats and FVB mice. This approach enables precise genome engineering to generate modifications such as point mutations, accurate insertions and deletions, and conditional knockouts and knock-ins. The same strategy can potentially be applied to many other species for which genetic engineering tools are needed.
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            Production of p53 gene knockout rats by homologous recombination in embryonic stem cells

            The use of homologous recombination to modify genes in embryonic stem (ES) cells provides a powerful means to elucidate gene function and create disease models1. Application of this technology to engineer genes in rats has previously been impossible in the absence of germline competent ES cells in this species. We have recently established authentic rat ES cells2, 3. Here we report the generation of the first gene knockout rats using the ES cell-based gene targeting technology. We designed a targeting vector to disrupt the tumor suppressor gene p53 (also known as Tp53) in rat ES cells via homologous recombination. p53 gene-targeted rat ES cells can be routinely generated. Furthermore, the p53 gene-targeted mutation in the rat ES cell genome can transmit through the germline via ES cell-rat chimeras to create p53 gene knockout rats. The rat is the most widely used animal model other than humans in biological research4–7. The establishment of gene targeting technology in rat ES cells, in combination with advances in genomics and the vast amount of research data on physiology and pharmacology in this species, now provides a powerful new platform for the study of human disease.
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              Genetic transformation of mouse embryos by microinjection of purified DNA.

              A recombinant plasmid composed of segments of herpes simplex virus and simian virus 40 viral DNA inserted into the bacterial plasmid pBR322 was microinjected into pronuclei of fertilized mouse oocytes. The embryos were implanted in the oviducts of pseudopregnant females and allowed to develop to term. DNA from newborn mice was evaluated by the Southern blotting technique for the presence of DNA homologous to the injected plasmid. Two of 78 mice in one series of injections showed clear homology, though the injected sequences had been rearranged. Band intensities from the two positive mice were consistent with the presence of donor DNA in most or all of the cells of the newborns. These results demonstrate that genes can be introduced into the mouse genome by direct insertion into the nuclei of early embryos. This technique affords the opportunity to study problems of gene regulation and cell differentiation in a mammalian system by application of recombinant DNA technology.
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                Author and article information

                Contributors
                ogura@rtc.riken.go.jp
                Journal
                Reprod Med Biol
                Reprod. Med. Biol
                10.1111/(ISSN)1447-0578
                RMB2
                Reproductive Medicine and Biology
                John Wiley and Sons Inc. (Hoboken )
                1445-5781
                1447-0578
                07 October 2018
                January 2019
                : 18
                : 1 ( doiID: 10.1111/rmb2.2019.18.issue-1 )
                : 34-39
                Affiliations
                [ 1 ] RIKEN BioResource Research Center Koyadai, Tsukuba Japan
                [ 2 ] Graduate School of Life and Environmental Sciences University of Tsukuba Tsukuba Japan
                [ 3 ] RIKEN Cluster for Pioneering Research Saitama Japan
                Author notes
                [*] [* ] Correspondence

                Atsuo Ogura, RIKEN BioResource Research Center, Koyadai, Tsukuba, Japan.

                Email: ogura@ 123456rtc.riken.go.jp

                Author information
                http://orcid.org/0000-0003-0447-1988
                Article
                RMB212241
                10.1002/rmb2.12241
                6332730
                30655719
                84d171df-4a11-4ce3-b304-4ff15f4e60ca
                © 2018 The Authors. Reproductive Medicine and Biology published by John Wiley & Sons Australia, Ltd on behalf of Japan Society for Reproductive Medicine.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 27 July 2018
                : 27 August 2018
                : 02 September 2018
                Page count
                Figures: 2, Tables: 1, Pages: 6, Words: 4520
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                rmb212241
                January 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.5.4 mode:remove_FC converted:15.01.2019

                embryo,fertilization,hamster,icsi,spermatozoon
                embryo, fertilization, hamster, icsi, spermatozoon

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