KrasLSLG12Vgeo mice contain a 5’ floxed-STOP followed by a G12V mutation in the Kras (v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) gene, and a 3’ IRES-&beta;-geo cassette. 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 activated in human tumors in pancreatic, colon, breast, and lung cancer. The unrecombined KrasLSLG12Vgeo allele is null. Hence, homozygous embryos die at midgestation as the Kras–/– mice. Cre-dependent removal of the floxed-STOP cassette allows concomitant expression of the KrasG12V oncoprotein along with expression of the chimeric Geo protein which has lacZ activity. Expression of the KrasG12V oncoprotein in germ line, by breeding to B6.C-Tg(CMV-cre)1Cgn/J mice (Stock No. <a href="https://www.jax.org/strain/006054">006054</a>), is embryonic lethal with embryos dying at around E9.5. In some cases partial recombination leading to mosaic embryos was observed. Embryonic lethality in these cases depended on the extent of KrasG12V oncoprotein expression. No such mosaic embryos were observed when crossing to the EIIa-Cre transgenic strain, which resulted in more efficient cleavage of the STOP cassette in the germ line. 

Ubiquitous expression of the KrasG12V oncoprotein in adult mice, by crossing to strains that express the inducible CreERT2 recombinase under the control of various ubiquitous promoters followed by exposure to a tamoxifen diet, selectively results in the induction of lung adenomas and adenocarcinomas. In some occasions, benign lesions have been observed in other tissues such as stomach and skin papillomas. Lung adenocarcinomas are also observed upon tracheal infection with Adeno-Cre particles. Treated mice display multifocal lesions in lungs, ranging from small patches of bronchiolo-alveolar hyperplasias to large bronchiolo-alveolar adenomas and adenocarcinomas that compress adjacent lung structures. Alveolar type II (ATII) cells yield malignant adenocarcinomas while Clara cells required an inflammatory response to yield hyperplasias and adenomas. 

When KrasLSLG12Vgeo mice were bred to bitransgenic Elas-tTA/tetO-Cre mice that express the Cre recombinase under the control of the Elastase promoter in a tet-off system, they developed pancreatic intraepithelial neoplasias (PanIN) with 100% incidence. They also developed full blown pancreatic ductal adenocarcinomas albeit with lesser frequency (20% by one year of age). Exposure of these mice to the antibiotic doxycyclin in order to prevent expression of the Cre recombinase until the mice reach adulthood, completely prevents the development of PanIN lesions in spite of wide spread expression of the KrasG12V oncoprotein in acinar cells. Induction of PanIN lesions and occasional PDAC tumors in these adult mice can be achieved by inducing pancreatic damage by treating them with low doses of caerulein.

Finally, embryonic fibroblasts (MEFs) from these mice do not undergo proliferative senescence and proliferate continuously as immortal cells upon Cre-mediated recombination of the KrasLSLG12Vgeo allele.

Mice bearing the Cre recombinase-inducible KrasLSLG12Vgeo allele may be useful for studying K-RAS driven lung adenocarcinomas.

Typically mice are recovered in 12-16 weeks. Contact Customer Service to place an order or for more information.

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