Uncoupling of G6b-B–Shp1–Shp2 disrupts platelet production. (A) Percentage of reticulated platelets following staining with Retic-Count (mean ± SEM, n = 6). (B) Clearance of platelets in WT and G6b-B diY/F mice, following labeling with IV NHS-biotin. (Bi) Biotin-labeled platelets measured by streptavidin-PE binding in tail vein–sampled whole blood (mean ± SEM, n = 5 or 6 per data point). (Bii) Rate of platelet elimination calculated from slope of loss of biotinylated platelets (mean ± SEM, n = 6). (Ci) Platelet recovery following anti-GPIbα antibody–mediated platelet depletion in WT and G6b-B diY/F mice (n = 8-20 per time point). (Cii) Platelet-recovery rate calculated from recovery data for WT and G6b-B diY/F mice between days 3 and 7 (mean ± SEM, n = 8-11). Representative images (Di) and quantification of the number of MKs (Dii) in hematoxylin and eosin (H&E)–stained spleen and femur sections from WT and G6b-B diY/F mice (mean ± SEM, n = 6 mice, 5 images per mouse). Arrowheads indicate MKs. Representative images of reticulin staining showing myelofibrosis of WT and G6b-B diY/F spleens and femurs (scale bars, 50 μm). (Diii) Spleen/body weight ratio in WT, G6b-B diY/F, and G6b KO mice (mean ± SEM, n = 22). ***P < .001.