Summary of the megakaryocytic and platelet phenotypes in the Shp-1, Shp-2, and SHp-1/Shp-2 conditional KO mice compared with the G6b-B KO. Whereas the Shp-1 and Shp-2 KO phenotypes differ significantly (Shp-1 exhibits decreased platelet function and Shp-2 increased platelet reactivity but abnormal megakaryopoiesis), the Shp-1/Shp-2 double KO has a severe phenotype that resembles the one observed in the G6b-B mice. Interestingly, G6b-B megakaryocytes show normal Mpl signaling compared with the Shp-1/Shp-2 double KO, in which Mpl signaling is defective.