Mucosal inflammation in mice treated with the HIF1α inhibitor PX-478 or with neuron-specific depletion of Myd88, Hif1a, or Vhl. (A) Related to Fig. 6, I–K: percentage of body weight change in PX-478- or vehicle-injected and 1×DSS-treated WT mice (DSS vehicle and PX-478, n = 19 per group). (B) Fecal lipocalin-2 in mice described in A (DSS vehicle and PX-478, n = 19 per group). (C) Percentage of total viable cells (left) and absolute cell counts (right) of mucosal Ly6g+ neutrophils in colons of mice described in A, quantified by FC (DSS vehicle and PX-478, n = 10 per group). Baseline shows the mean value for PX-478–injected mice on water (n = 1). (D) Related to Fig. S10, C–E: percentage of body weight change in tamoxifen- and 1×DSS-treated SLICK-HER-CreHif1afl/fl (Cre+) or Hif1afl/fl (Cre–) littermates (DSS Cre– and Cre+, n = 19–23 per group). (E) Fecal lipocalin-2 in mice described in D (DSS Cre– and Cre+, n = 26–31 per group). (F) Percentage of total viable cells (left) and absolute cell counts (right) of mucosal Ly6g+ neutrophils in colons of mice described in D, quantified by FC (DSS Cre– and Cre+, n = 20 per group). Baseline shows the mean value for tamoxifen- and water-treated Hif1afl/fl littermates (water Cre–, n = 13). P values above each column show statistical differences against baseline. (G) Related to Fig. S10, F–H: percentage of body weight change in tamoxifen- and 1×DSS-treated SLICK-HER-CreMyd88fl/fl (Cre+) and Myd88fl/fl (Cre–) littermates (DSS Cre– and Cre+, n = 18 per group). (H) Fecal lipocalin-2 levels in mice described in G (DSS Cre– and Cre+, n = 18 per group). (I) Percentage of total viable cells (left) and absolute cell counts (right) of mucosal Ly6g+ neutrophils in colons of mice described in G, quantified by FC (DSS Cre– and Cre+, n = 15–18 per group). Baseline shows the mean value for tamoxifen- and water-treated Myd88fl/fl littermates (water Cre–, n = 12). P values above each column show statistical differences against baseline. (J) Complementary to Fig. 6, L–P: percentage of body weight change in tamoxifen- and 3×DSS-treated SLICK-HER-CreVhlfl/fl (Cre+) and Vhlfl/fl (Cre–) littermates (DSS Cre– and Cre+, n = 8 per group). (K) Fecal lipocalin-2 in mice described in J (DSS Cre– and Cre+, n = 35–41 per group). (L) Percentage of total viable cells (left) and absolute cell counts (right) of mucosal Ly6g+ neutrophils in colons of mice described in J, quantified by FC (DSS Cre– and Cre+, n = 7–19 per group). Baseline shows the mean value for tamoxifen- and water-treated Vhlfl/fl littermates (water Cre–, n = 5–9). P values above each column show statistical differences against baseline. All graphs show the mean ± SEM, n—mouse. Data are representative of at least two independent experiments with similar results. Data are pooled from two to four smaller experiments. Statistical analyses: unpaired Student’s t test (C, F, I, and L), multiple t test (A, D, G, and J), and two-way ANOVA for multiple comparisons (B, E, H, and K), *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, and ****P ≤ 0.0001.
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