Figure 1.
Disease phenotype characterization of JAK2-V617F (VF) and JAK2-V617F;Dnmt3aΔ/Δ (VF;DmΔ/Δ) mice. (A) Schematic drawing of induction with tamoxifen injections for 4 weeks (red box) and experimental procedures. (B) Analysis of Cre-mediated excision of Dnmt3a. Left panel shows representative gel from Bioanalyzer DNA chip, with bands corresponding to floxed (fl) and deleted (Δ) Dnmt3a alleles. Right panel shows quantification of fl and Δ Dnmt3a alleles (n = 4 per genotype). (C) Time course of nonfasting blood glucose levels (n = 5-7 mice per genotype). (D) Time course of peripheral blood counts (n = 5-7 mice per genotype). (E) Spleen weight at terminal workup after 16 weeks postinduction. (F) BM cellularity per 4 bones (n = 4-5 mice per genotype). (G) Frequencies of HSPCs in BM and spleen at terminal workup after 16 weeks of treatment (n = 4-5 mice per genotype). (H) Analysis of erythroid progenitor’s frequencies in BM and spleen at terminal analysis. (I) Quantification BM fibrosis and osteosclerosis (n = 4-5 mice per genotype). The degree of myelofibrosis was scored and assigned on a scale from MF-0 to MF-3. Osteosclerosis was scored as present or absent. All data are presented as mean ± standard error of the mean. Two-way analyses of variance (ANOVA) with subsequent Tukey (B-C) and Dunnett posttest (G; erythroid progenitors), 1-way ANOVA with subsequent Tukey posttest (D,E,G; Ter119+ cells, H) or unpaired t test with Welch correction (F) were used. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001.