HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Megakaryocyte-restricted MYH9 inactivation dramatically affects hemostasis while preserving platelet aggregation and secretion

Mutations in the MYH9 gene encoding the nonmuscle myosin heavy chain IIA result in bleeding disorders characterized by a macrothrombocytopenia. To understand the role of myosin in normal platelet func-tions and in pathology, we generated mice with disruption of MYH9 in megakaryo-cytes. MYH9 mice displayed macro-thrombocytopenia with a strong increase in bleeding time and absence of clot retraction. However, platelet aggregation and secretion in response to any agonist were near normal despite absence of ini-tial platelet contraction. By contrast, inte-grin outside-in signaling was impaired, a