Effect of VPAC1 inhibition in mouse and human thrombocytopenia due to GATA1 defect. (A) Platelet count in blood following administration of 23A11 (■) on days 0, 3, and 7 or PBS (●) in ΔneoΔHS GATA1-deficient mice (left panel). Each point represents the mean platelet count from 4 (■) or 3 (●) mice plus or minus SD. **P < .01; #P < .001 by ANOVA. The plasma TPO levels from the same GATA1-deficient mice treated with 23A11 (■) or PBS (●) at the indicated days (right panel). Each point represents the mean TPO value from 4 (■) or 3 (●) mice plus or minus SD. (B) Histograms demonstrate the DNA ploidy distribution of CD41⁺ megakaryocytes in vitro–differentiated from Sca1⁺ cells isolated from bone marrow from ΔneoΔHS mice in the absence (left) or presence (right) of 23A11 on day 12. (C) Histograms demonstrate the DNA ploidy distribution of CD41⁺ megakaryocytes differentiated from CD34⁺ cells from bone marrow of the GATA1-D218Y patient in the absence (left) or presence of 23A11 (right) on day 12. FACS results are representative of 2 separate analyses.