Absence of Rac1 and Cdc42 leads to macrothrombocytopenia. (A) Western blot analysis of Rac1 and Cdc42 expression in wild-type (wt) and Rac1/Cdc42^−/− platelets generated by the Mx-Cre (left) or the PF4-Cre (right) system. GPIIIa expression was used as loading control. Analysis of peripheral platelet counts (B) and mean platelet volume (C) of wt (black), Rac1^−/− (dark gray), Cdc42^−/− (light gray), and Rac1/Cdc42^−/− (patterned) mice (n = 5 per group; ***P < .001). (D-E) Rac1/Cdc42^−/− platelets are increased in size. Representative scanning (D) and transmission (E) electron microscopy pictures from wt and Rac1/Cdc42^−/− platelets are depicted. Bars, 5 and 2 µm.