Co-ablation of p53 decreases apoptosis and the survival of Dicer^Δ/Δ mice.

<p><b>A</b>) Hematoxylin and eosin staining of skin tissue sections of 5-month old mice. Control (K5-Cre+ transgene) was similar in appearance to wildtype control samples, whereas ablation of <i>Dicer</i> showed reduced and misshapen follicle morphology, with increased epithelial thickening, mitotic figures (arrow), and incidence of apoptosis (arrowheads). Ablation of p53 did not alter follicle dysmorphology seen in Dicer^Δ/Δ mice (upper right panel), though epithelial cellularity was more pronounced in some regions (see star on bottom right side panel) and fewer apoptotic events were noted. Scale bars equal 100 microns. B) Measurements of epidermal thickness in microns for control skin (white bar), Dicer-ablated skin (gray bar), and Dicer, p53 co-ablated skin (black bar). Bars represent average thickness, with standard deviation shown. Asterisks indicate p values<0.01 between control and Dicer-ablated skin or control and Dicer, p53 co-ablated skin. <b>C</b>) Average number of apoptotic cells observed in 40X field. No apoptotic figures were seen in control tissues (white bar) whereas apoptosis was increases in Dicer-ablated skin (gray bar) and in Dicer, p53 co-ablated skin (black bar) relative to controls. Apoptosis was decreased in Dicer-ablated skin co-deleted for functional p53. Asterisks indicate p values<0.01. <b>D</b>) Average number of mitotic figures seen in 40X field. Mitosis was increased in Dicer-ablated skin (gray bar) and in Dicer, p53 co-ablated skin (black bar) relative to controls (white bar). Asterisks indicate p values<0.01 between control and Dicer-ablated skin or control and Dicer, p53 co-ablated skin. <b>E</b>) Immuno-staining for the proliferation antigen Ki-67 confirms increased cell proliferation in the epidermis of <i>Dicer</i>-ablated mice in the presence or absence of functional <i>p53</i>. Scale bars equal 100 microns. <b>F</b>) PCR-based genotyping of tissues harvested from Dicer conditional, p53 conditional mice in the absence (Dicer^c/c, p53^c/c) or presence (Dicer^Δ/Δ p53^Δ/Δ) of the K5-Cre transgene. Deletion of functional Dicer and p53 alleles is detected specifically in the skin and tumor tissues of K5-Cre+ mice. <b>G</b>) Kaplan-Meier survival curves for Dicer-ablated mice bearing one (purple; n = 17), two (red; n = 14), or no (black; n = 45) functional alleles of p53. Ablation of both <i>Dicer</i> and <i>p53</i> in the skin greatly reduced viability of these mice relative to mice ablated for <i>Dicer</i> in skin (p<0.01) or mice ablated for <i>Dicer</i> and one allele of <i>p53</i> in skin (p<0.01).