Hypoallelic mice have increased proliferation and cell cycle defects in HSCs and myeloid progenitor-enriched compartments. (A) BrdU was administered to mark cells that entered S phase, and 7-amino-actinomycin D (7AAD) indicated DNA content. LSK and MP cells from MDS/MPN hypoallelic mice (backgate analysis shown at left) contain more dividing cells (43.6% and 31.5%, respectively) than age-matched wild-type controls (12.1% and 19.4%, respectively). Percentages shown represent averages of all samples; n = 3 in each group. Both NR4A1^−/−NR4A3^+/− (n = 1, at 11 months) and NR4A1^+/−NR4A3^−/− mice (n = 2, at 4-6 months) were used for this assay. (B) Propidium iodide incorporation revealed a larger number of proliferating cells (S + G₂/M) in CD11b⁺/Gr-1^low/− immature myeloid cells of MDS/MPN hypoallelic animals (30.3%) compared with age-matched controls (18.1%). Percentages shown represent averages of all samples; n = 4 for in each group. Both NR4A1^−/−NR4A3^+/− (n = 1, at 10.5 months) and NR4A1^+/−NR4A3^−/− mice (n = 3, at 3-5 months) were used for this assay. (C-D) Bar charts represent data shown in panels A and B, respectively. *P < .01. Error bars represent SEM.