DOX-dependent suppression of TPA-induced COX-2 expression by shCox2 in mice homozygous for the <i>Cox2</i> gene.

<p>(<b>A</b>) Double transgenic shCox2/C3 mice, which have two wild type <i>Cox2</i> alleles, were maintained on either a control (no DOX) or a DOX-supplemented diet (+DOX) for 12 days, then painted with TPA on the back. 24 hours after TPA administration the mice were euthanized and skin extracts were assayed for GFP and COX-2 protein by Western blotting. Quantification is from three independent experiments. The COX-2 signal was normalized to the GAPDH loading control. Data are means +/− S.D. (***p<0.001). (<b>B</b>) COX-2 (upper panels) and GFP (lower panels) immunohistochemistry in skin of untreated shCox2/C3 mice (left panels), 24 hours after TPA administration to shCox2/C3 mice maintained on a DOX-free diet (center panels) and 24 hours after TPA treatment of shCox2/C3 mice maintained for 12 days on a DOX-supplemented diet (right panels). COX-2 staining is visible as brown patches (white arrow) in the basal epithelium. (<b>C</b>) H&E stain to visualize leukocytes in skin sections from double transgenic shCox2/C3 mice treated with TPA and/or DOX as in B. The graph depicts quantification of leukocytes in the dermis. Quantification is from two independent experiments. Data are means +/− S.D. (**p<0.01). The scale bar indicates 50 µm.