An inducible mouse model for skin cancer reveals distinct roles for gain- and loss-of-function p53 mutations
J. Clin. Invest. Carlos Caulin, et al. 117:1893 doi:10.1172/JCI31721 [Go to this article.]

Figure 2
Activation of the p53^R172H allele contributes to tumor initiation and malignant progression of skin tumors. (A) Schematic representation of the neo-p53^R172H allele showing exons 4 and 5, the presence of the neo cassette in intron 4, and primers R172H reverse and R172H forward (PM1 and PM2, respectively; see Methods), which were used for PCR analysis of the p53 allele. The neo cassette prevents expression of the p53^R172H allele (C. Caulin, D.R. Roop, and G. Lozano, unpublished observations). Asterisks indicate mutation in exon 5 for p53^R172H. (B) Schematic representation of the p53^f allele showing loxP sites in introns 1 and 10 and primers PF1 and PF2 (26) that were used to analyze deletion of exons 2–10. (C) Kinetics of tumor formation in K-ras–p53^R172H/WT mice (K-p53^R172H/WT; n = 22) and K-ras–p53^f/WT mice (K-p53^f/WT; n = 21). K-ras–p53^WT/WT mice (K-p53^WT/WT; n = 17) were used as controls. Tumor formation was evaluated by the average number of tumors developed per mouse after the initial treatment with TPA. (D) Kinetics of carcinoma formation. Each time point represents percentage of mice bearing carcinomas. (E) Kinetics of tumor formation in K-ras–p53^R172H/f mice (K-p53^R172H/f; n = 16) and K-ras–p53^f/f mice (K-p53^f/f; n = 22). (F) Kinetics of carcinoma formation in K-ras–p53^R172H/f and K-ras–p53^f/f mice. (G) Activation of the p53^R172H, p53^f, and K-ras^G12D alleles in papillomas and carcinomas. Primers PM1 and PM2 were used to analyze activation of the p53^R172H allele. Primers PF1 and PF2 were used to analyze deletion of the loxP-flanked sequences in the p53^f allele. Primers P1 and P2 were used to analyze activation of the K-ras^G12D allele. DNA purified from spleen (Sp; lane 16) of a K-ras–p53^R172H/WT mouse was used as a control and only generated the band corresponding to p53^WT or K-ras^WT alleles.