title: Deregulated Nras expression in knock-in animals harboring a gammaretroviral long terminal repeat at the Nras/Csde1 locus.
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.
authors: Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark. fsp@mb.au.dk
authors: Borja
authors: B
authors: Ballarín-González
authors: Louise Berkhoudt
authors: LB
authors: Lassen
authors: Randi
authors: R
authors: Jessen
authors: Annette
authors: A
authors: Füchtbauer
authors: Ernst-Martin
authors: EM
authors: Füchtbauer
authors: Finn Skou
authors: FS
authors: Pedersen
mesh_terms: D000483:Alleles; D000818:Animals; D017988:Gammaretrovirus / Q000235:genetics* / Q000378:metabolism; D011905:Genes, ras / Q000235:genetics*; D051379:Mice; D016254:Mutagenesis, Insertional; D020079:Terminal Repeat Sequences; D016662:Virus Integration