Proceedings of the National Academy of Sciences · 1992 · 693 citations · 24 references
MedicineGeneticsMolecular BiologyGene ExpressionMolecular OncologyRecombinationOncogene ActivationOncogene AmplificationProto-oncogene ActivationTransgene ConstructionTransgene DesignTransgene Expression ControlCre-lox Recombination SystemsRecombinase ProteinsRecombinase Recognition SitesTransgene TargetingTransgenic MiceTransgenic Mouse Cancer ModelsTransgenic Mouse ModelsTransgenic Mouse Production
The study presents an efficient, accurate method for controlled in vivo transgene modulation via site‑directed recombination. Seven founder lines carrying a lens‑specific promoter and SV40 large T antigen separated by a Cre‑targeted stop cassette were crossed with mice expressing Cre under lens‑specific or CMV promoters to enable site‑specific deletion. All double‑transgenic offspring developed lens tumors, confirming that Cre‑mediated deletion of the stop cassette activates large T antigen expression and drives tumorigenesis.
An efficient and accurate method for controlled in vivo transgene modulation by site-directed recombination is described. Seven transgenic mouse founder lines were produced carrying the murine lens-specific alpha A-crystallin promoter and the simian virus 40 large tumor-antigen gene sequence, separated by a 1.3-kilobase-pair Stop sequence that contains elements preventing expression of the large tumor-antigen gene and Cre recombinase recognition sites. Progeny from two of these lines were mated with transgenic mice expressing the Cre recombinase under control of either the murine alpha A-crystallin promoter or the human cytomegalovirus promoter. All double-transgenic offspring developed lens tumors. Subsequent analysis confirmed that tumor formation resulted from large tumor-antigen activation via site-specific, Cre-mediated deletion of Stop sequences.
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RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination
Marjorie A. Oettinger, David G. Schatz, Carolyn Gorka et al. · Science · 1990 · 1.5K citations
The V(D)J recombination activating gene, RAG-1
David G. Schatz, Marjorie A. Oettinger, David Baltimore · Cell · 1989 · 1.2K citations · Full text