ArticleProceedings of the National Academy of Sciences of the United States of America2013
Controlled insertional mutagenesis using a LINE-1 (ORFeus) gene-trap mouse model.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Transposable elements shape the evolution of mammalian development.Nature reviews. Genetics · 2021Review
- A potential new mechanism for pregnancy loss: considering the role of LINE-1 retrotransposons in early spontaneous miscarriage.Reproductive biology and endocrinology : RB&E · 2020Review
- Five months of voluntary wheel running downregulates skeletal muscle LINE-1 gene expression in rats.American journal of physiology. Cell physiology · 2019Article
- Comprehensive Scanning Mutagenesis of Human Retrotransposon LINE-1 Identifies Motifs Essential for Function.Genetics · 2019Article
- Identification of RNase-sensitive LINE-1 Ribonucleoprotein Interactions by Differential Affinity Immobilization.Bio-protocol · 2019Article
- Advances in functional genetic screening with transposons and CRISPR/Cas9 to illuminate cancer biology.Current opinion in genetics & development · 2018Review
- A conserved role for the ESCRT membrane budding complex in LINE retrotransposition.PLoS genetics · 2017Article
- Meeting Report: The Role of the Mobilome in Cancer.Cancer research · 2016Article
- Affinity proteomics to study endogenous protein complexes: pointers, pitfalls, preferences and perspectives.BioTechniques · 2015Article
- A role for retrotransposon LINE-1 in fetal oocyte attrition in mice.Developmental cell · 2014Article
- Exploiting the power of LINE-1 retrotransposon mutagenesis for identification of genes involved in embryonic stem cell differentiation.Stem cell reviews and reports · 2014Article
- Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
A codon-optimized mouse LINE-1 element, ORFeus, exhibits dramatically higher retrotransposition frequencies compared with its native long interspersed element 1 counterpart. To establish a retrotransposon-mediated mouse model with regulatable and potent mutagenic capabilities, we generated a tetracycline (tet)-regulated ORFeus element harboring a gene-trap cassette. Here, we show that mice expressing tet-ORFeus broadly exhibit robust retrotransposition in somatic tissues when treated with doxycycline. Consistent with a significant mutagenic burden, we observed a reduced number of double transgenic animals when treated with high-level doxycycline during embryogenesis. Transgene induction in skin resulted in a white spotting phenotype due to somatic ORFeus-mediated mutations that likely disrupt melanocyte development. The data suggest a high level of transposition in melanocyte precursors and consequent mutation of genes important for melanoblast proliferation, differentiation, or migration. These findings reveal the utility of a retrotransposon-based mutagenesis system as an alternative to existing DNA transposon systems. Moreover, breeding these mice to different tet-transactivator/reversible tet-transactivator lines supports broad functionality of tet-ORFeus because of the potential for dose-dependent, tissue-specific, and temporal-specific mutagenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.