TITLE

Deregulated Nras Expression in Knock-In Animals Harboring a Gammaretroviral Long Terminal Repeat at the Nras/Csde1 Locus

AUTHOR(S)
Ballarín-González, Borja; Lassen, Louise Berkhoudt; Jessen, Randi; Füchtbauer, Annette; Füchtbauer, Ernst-Martin; Pedersen, Finn Skou
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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.
ACCESSION #
87624219

 

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