Figure 7.

p53 deficiency rescues proliferative defects and hyperpigmentation of TRF1^Δ/Δ K5-Cre mice but results in increased skin cancer. (A, left) TRF1^Δ/ΔK5-Cre p53^−/− mice grow hair. (Right) TRF1^Δ/ΔK5-Cre p53^−/− mice do not show skin hyperpigmentation. (B) Kaplan-Meyer survival curves of the different mouse cohorts. n = mice of each genotype included in the analysis. P-value for statistical comparisons between genotypes was calculated using log rank test. (C) Weight gain of the different mouse cohorts. n = mice of each genotype used for the analysis. (D) TRF1^Δ/ΔK5-Cre p53^−/− mice develop nail atrophy and dysplastic epithelium at the proximal and ventral nail fold. (E) TRF1^Δ/ΔK5-Cre p53^−/− mice develop oral leukoplakia characterized by severe epithelia hyperplasia, hyperkeratosis, and dermis invasion by basal keratinocytes (arrows). (F) SCCs in tail and ear skin of TRF1^Δ/ΔK5-Cre p53^−/− mice. (Top panel) Macroscopic appearance of tail and ear skin in a TRF1^Δ/ΔK5-Cre p53^−/− P42 mouse. (Bottom panel) Histopathological analysis of the SCC shows high mitotic index, pleomorphic cells with bizarre nuclei, and aberrant mitosis (arrowhead). Nest of epithelial tumoral cells invade the ear dermis (arrows). (G) Multinucleated giant cells and anaphase bridges are observed in SCC. n = mice or SCC analyzed. The total number of scored cells is indicated. The P-value is calculated by the Student's t-test. (H) Representative images of multinucleated giant cells and anaphase bridges.