Spontaneous development of papillomas in mice carrying a <i>LSL-K-Ras<sup>G12D</sup></i> allele on a <i>K14-Cre:ER</i> background.

<p>(<b>A</b>) Within weeks of birth <i>LSL-K-Ras<sup>G12D</sup>;K14-Cre:ER</i> mice developed papillomas, predominantly in the oral epithelium (upper panel, 78 of 78 mice observed) and occasionally at additional sites such as the side of the head (lower panel, see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0017143#pone-0017143-t001" target="_blank">Table 1</a> for incidence). (<b>B</b>) Hematoxylin and eosin staining (H&E) of oral epithelium shows typical staining in <i>LSL-K-Ras<sup>G12D</sup></i> mice (upper panel) and large intensely staining growths in <i>LSL-K-Ras<sup>G12D</sup>;K14-Cre:ER</i> mice (lower panels). Staining for the proliferation marker Ki-67 revealed low levels in <i>LSL-K-Ras<sup>G12D</sup></i> but elevated levels in the proximal regions of papillomas from <i>LSL-K-Ras<sup>G12D</sup>;K14-Cre</i> mice. (<b>C</b>) Genotyping of genomic DNA from isolated oral papillomas using a wildtype-allele specific primer pair (Wt) and floxed transcription termination cassette-specific primer pair (LSL) showed a reduction in the abundance of LSL amplicon within four independent papillomas (upper panel). This was confirmed by qPCR using the same primer pairs (lower panel). (<b>D</b>) Kaplan-Meier survival curve of <i>LSL-K-Ras<sup>G12D</sup></i> and <i>LSL-K-Ras<sup>G12D</sup>;K14-Cre:ER</i> mice shows the dramatic differences between each mouse strain. Median survival for <i>LSL-K-Ras<sup>G12D</sup>;K14-Cre:ER</i> mice was determined to be 51 days.</p>