KrasFSFG12V mice contain a 5’ frt-flanked STOP-neo cassette, followed by a G12V mutation in the Kras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) gene. Ras genes are small GTPases that act downstream of receptors and nonreceptor tyrosine protein kinases in multiple pathways to transfer information to the nucleus. K-ras has been found to be primarily activated in human tumors in pancreatic, colon, and lung cancer. The unrecombined KrasFSFG12V allele is null. Hence, homozygous KrasFSFG12V embryos die at midgestation as the Kras–/– mice. When bred to mice expressing FLP Recombinase, removal of the frt-flanked STOP cassette allows expression of KrasG12V, commonly found in human tumors.
Tracheal infection of these KrasFSFG12V mice with Adeno-FLP particles induces lung adenomas and adenocarcinomas with an incidence and latency similar to that observed in the KrasLSLG12Vgeo mice (Stock No. 026924) infected with Adeno-Cre particles.
Breeding to bitransgenic Elas-tTA/tetO-FLP mice that express FLP recombinase under the control of the elastase promoter in a tet-off system allows selective expression of the KrasG12V oncoprotein in cells of pancreatic acinar lineage. Untreated mice develop PanIN lesions and pancreatic ductal adenocarcinomas with an incidence and latency similar to that observed with KrasLSLG12Vgeo mice carrying the Elas-tTA/tetO-Cre transgenes.
Crossing KrasFSFG12V mice with strains carrying floxed alleles of targets with potential therapeutic value, allows the temporal and spatial separation of tumor development and target ablation. This strategy makes it possible to determine the therapeutic properties of the target in a well established tumors.
