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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Main Authors: Borja Ballarín-González, Louise Berkhoudt Lassen, Randi Jessen, Annette Füchtbauer, Ernst-Martin Füchtbauer, Finn Skou Pedersen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
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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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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