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      Retroviral Elements and Their Hosts: Insertional Mutagenesis in the Mouse Germ Line

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          Abstract

          The inbred mouse is an invaluable model for human biology and disease. Nevertheless, when considering genetic mechanisms of variation and disease, it is important to appreciate the significant differences in the spectra of spontaneous mutations that distinguish these species. While insertions of transposable elements are responsible for only ~0.1% of de novo mutations in humans, the figure is 100-fold higher in the laboratory mouse. This striking difference is largely due to the ongoing activity of mouse endogenous retroviral elements. Here we briefly review mouse endogenous retroviruses (ERVs) and their influence on gene expression, analyze mechanisms of interaction between ERVs and the host cell, and summarize the variety of mutations caused by ERV insertions. The prevalence of mouse ERV activity indicates that the genome of the laboratory mouse is presently behind in the “arms race” against invasion.

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          Most cited references113

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          Mobile elements: drivers of genome evolution.

          Mobile elements within genomes have driven genome evolution in diverse ways. Particularly in plants and mammals, retrotransposons have accumulated to constitute a large fraction of the genome and have shaped both genes and the entire genome. Although the host can often control their numbers, massive expansions of retrotransposons have been tolerated during evolution. Now mobile elements are becoming useful tools for learning more about genome evolution and gene function.
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            Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting.

            Imprinted genes are epigenetically marked during gametogenesis so that they are exclusively expressed from either the paternal or the maternal allele in offspring. Imprinting prevents parthenogenesis in mammals and is often disrupted in congenital malformation syndromes, tumours and cloned animals. Although de novo DNA methyltransferases of the Dnmt3 family are implicated in maternal imprinting, the lethality of Dnmt3a and Dnmt3b knockout mice has precluded further studies. We here report the disruption of Dnmt3a and Dnmt3b in germ cells, with their preservation in somatic cells, by conditional knockout technology. Offspring from Dnmt3a conditional mutant females die in utero and lack methylation and allele-specific expression at all maternally imprinted loci examined. Dnmt3a conditional mutant males show impaired spermatogenesis and lack methylation at two of three paternally imprinted loci examined in spermatogonia. By contrast, Dnmt3b conditional mutants and their offspring show no apparent phenotype. The phenotype of Dnmt3a conditional mutants is indistinguishable from that of Dnmt3L knockout mice, except for the discrepancy in methylation at one locus. These results indicate that both Dnmt3a and Dnmt3L are required for methylation of most imprinted loci in germ cells, but also suggest the involvement of other factors.
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              Repbase update: a database and an electronic journal of repetitive elements.

              J Jurka (2000)
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                Author and article information

                Journal
                PLoS Genet
                pgen
                PLoS Genetics
                Public Library of Science (San Francisco, USA )
                1553-7390
                1553-7404
                January 2006
                27 January 2006
                : 2
                : 1
                : e2
                Affiliations
                [1]
                Author notes
                * To whom correspondence should be addressed. E-mail: dmager@ 123456bccrc.ca

                Irina A. Maksakova, Mark T. Romanish, Liane Gagnier, Catherine A. Dunn, Louie N. van de Lagemaat, and Dixie L. Mager are at the Terry Fox Laboratory, BC Cancer Agency, Vancouver, British Columbia, Canada, and Department of Medical Genetics, University of British Columbia, Canada.

                Article
                05-PLGE-RV-0111R2 plge-02-01-01
                10.1371/journal.pgen.0020002
                1331978
                16440055
                f89bfcf2-f425-49ee-8b62-286a5c95ea85
                Copyright: © 2006 Maksakova et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                Page count
                Pages: 10
                Categories
                Review
                Evolution
                Pathology
                Genetics/Genomics
                Genetics/Disease Models
                Genetics/Epigenetics
                Animals
                Viruses
                Custom metadata
                Maksakova IA, Romanish MT, Gagnier L, Dunn CA, van de Lagemaat LN, et al. (2006) Retroviral elements and their hosts: Insertional mutagenesis in the mouse germ line. PLoS Genet 2(1): e2.

                Genetics
                Genetics

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