Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus.
To investigate mechanisms and phenotypic effects of insertional mutagenesis by gammaretroviruses, we have developed mouse lines containing a single Akv 1-99 long terminal repeat (LTR) and a floxed PGK/Tn5 neomycin cassette at the Nras proto-oncogene at positions previously identified as viral integr...
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Public Library of Science (PLoS)
2013-01-01
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Series: | PLoS ONE |
Online Access: | http://europepmc.org/articles/PMC3572152?pdf=render |
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author | Borja Ballarín-González Louise Berkhoudt Lassen Randi Jessen Annette Füchtbauer Ernst-Martin Füchtbauer Finn Skou Pedersen |
author_facet | Borja Ballarín-González Louise Berkhoudt Lassen Randi Jessen Annette Füchtbauer Ernst-Martin Füchtbauer Finn Skou Pedersen |
author_sort | Borja Ballarín-González |
collection | DOAJ |
description | To investigate mechanisms and phenotypic effects of insertional mutagenesis by gammaretroviruses, we have developed mouse lines containing a single Akv 1-99 long terminal repeat (LTR) and a floxed PGK/Tn5 neomycin cassette at the Nras proto-oncogene at positions previously identified as viral integration sites in Akv 1-99 induced tumors. The insert did not compromise the embryonic development, however, the cassette had an effect on Nras expression in all tissues analyzed. Cre-mediated excision of the PGK/Tn5 neomycin cassette in two of the lines caused upregulation of Nras. Altogether, the knock-in alleles are characterized by modulation of expression of the target gene from more than ten-fold upregulation to three-fold downregulation and exemplify various mechanisms of deregulation by insertional mutagenesis. LTR knock-in mice may serve as a tool to investigate mechanisms of retroviral insertional mutagenesis and as a way of constitutive or induced modulation of expression of a target gene. |
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institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-11T04:17:40Z |
publishDate | 2013-01-01 |
publisher | Public Library of Science (PLoS) |
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spelling | doaj.art-6352d533bc8d46d188d090b649b97ff02022-12-22T01:21:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0182e5602910.1371/journal.pone.0056029Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus.Borja Ballarín-GonzálezLouise Berkhoudt LassenRandi JessenAnnette FüchtbauerErnst-Martin FüchtbauerFinn Skou PedersenTo investigate mechanisms and phenotypic effects of insertional mutagenesis by gammaretroviruses, we have developed mouse lines containing a single Akv 1-99 long terminal repeat (LTR) and a floxed PGK/Tn5 neomycin cassette at the Nras proto-oncogene at positions previously identified as viral integration sites in Akv 1-99 induced tumors. The insert did not compromise the embryonic development, however, the cassette had an effect on Nras expression in all tissues analyzed. Cre-mediated excision of the PGK/Tn5 neomycin cassette in two of the lines caused upregulation of Nras. Altogether, the knock-in alleles are characterized by modulation of expression of the target gene from more than ten-fold upregulation to three-fold downregulation and exemplify various mechanisms of deregulation by insertional mutagenesis. LTR knock-in mice may serve as a tool to investigate mechanisms of retroviral insertional mutagenesis and as a way of constitutive or induced modulation of expression of a target gene.http://europepmc.org/articles/PMC3572152?pdf=render |
spellingShingle | Borja Ballarín-González Louise Berkhoudt Lassen Randi Jessen Annette Füchtbauer Ernst-Martin Füchtbauer Finn Skou Pedersen Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus. PLoS ONE |
title | Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus. |
title_full | Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus. |
title_fullStr | Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus. |
title_full_unstemmed | Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus. |
title_short | Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus. |
title_sort | deregulated nras expression in knock in animals harboring a gammaretroviral long terminal repeat at the nras csde1 locus |
url | http://europepmc.org/articles/PMC3572152?pdf=render |
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