Effects of Mdm2 gene dosage and 5-fluorouracil on p53 levels and hematologic phenotypes. Example (A) and quantitation (B) of p53 immunostaining in BM sections from animals with reduced Mdm2 activity (Mdm2^puro/Δ7-9) compared with control (+/+) animals. For panel B, n = 5 mice per group, mean number of p53-positive cells per hpf ± SEM is shown, 6 hpf per animal. Example (C) and quantitation (D) of megakaryocyte abundance in BM sections from Mdm2^puro/Δ7-9 and +/+ animals. For panel D, n = 3 animals per genotype, mean number of megakaryocytes per hpf ± SEM is shown, 10 hpf per animal. (E) Quantitation of VWF-positive cells in BM sections from nonmutant (+/+) and Mdm2 mutant (Mdm2^puro/Δ7-9) animals (n = 4 animals per genotype, mean number of VWF-positive cells with large nuclei per hpf is shown ± SEM, 10 hpf per animal). (F-G) RBC and platelet counts (per μL) after administration of 5-fluorouracil to control (+/+, n = 6) and p53-deficient (Trp53^ko/ko, n = 4) animals. Values before 5-fluorouracil treatment (white bars), 11 days after treatment (black bars), and 25 days after treatment (gray bars) are shown ± SEM. P values are based on a 2-tailed t test (B,D,E) or multiple regression where sex and genotype are factors (F-G), **P < .01, ***P < .001; NS indicates not significant. Scale bars: 75μM (A); 50μM (C).