Figure 4.

The effect of low Cre expression. Histological analysis of haematoxylin and eosin-stained tissues from K-ras^+/G12D mice dosed intraperitoneally with 1–10 µg of tamoxifen, including (A) a thymic lymphoma (original magnification × 400), (B) multiple adenocarcinomas of the lung (original magnification × 25), and (C) a lip squamous papilloma with dysplasia (original magnification × 25). (D) Survival of undosed K-ras^+/+ and K-ras^+/G12D mice. The median survival for K-ras^+/G12D mice was 18–20 weeks. Log-rank (Mantel–Cox) test: p > 0.0001. (E) Representative example of the gross appearance of oral tumours that ‘spontaneously’ developed in undosed K-ras^+/G12D mice. (F) Histological analysis of haematoxylin and eosin-stained section representative of the ‘spontaneous’ oral papillomas observed (original magnification × 25). (G) PCR analysis of Cre-mediated removal of the floxed ‘stop’ cassette (and hence expression of the activated K-ras^G12D) on gDNA from selected tissues of K-ras^+/G12D mice that spontaneously developed tumours. Mouse 51.1a, which developed a thymic lymphoma and multiple pulmonary adenocarcinomas, showed activated K-ras^G12D in the thymus, lung, and liver. Mouse 29.4e, which developed an oral papilloma and multiple pulmonary adenocarcinomas, showed activated K-ras^G12D in the lip and lung