Deletion of ERp5 in the megakaryocyte lineage results in mild macrothrombocytopenia. (A) Western blot of ERp5 in resting platelet lysates from control (ERp5^fl/fl) and CKO (Pf4Cre⁺/ERp5^fl/fl) mice, demonstrating ERp5 deletion in platelets. (B) Immunostaining of ERp5 in platelets from control and CKO mice after their adhesion to fibrinogen, without (resting) or with stimulation with thrombin (IIα). Differential interference contrast (DIC) (top) and staining with an anti-ERp5 Alexa 488 antibody (bottom). Representative images, n = 2 per genotype. (C) Peripheral platelet count and mean platelet volume (MPV) in control (gray column) and CKO mice (red column), n = 16 to 18 mice per genotype. (D) Percentage of reticulated (thiazole orange–positive) platelets in control and CKO mice. (E) Ultrastructure of resting platelets isolated from control and CKO mice. Representative TEM images showing increased platelet size in CKO mice. n = 4 mice per genotype for thiazole orange staining and TEM, mean ± standard error of the mean (SEM), Student t test. ∗P < .05, ∗∗P < .005. Scale bar, 10 μm (B) and 2 μm (E).