Integrin α 2-deficient mice develop normally, are fertile, but display partially defective platelet interaction with collagen

The integrin α 2-subunit was ablated in mice by targeted deletion of the ITGA2 gene. α 2-Deficient animals develop normally, are fertile, and reproduce. Surprisingly, no obvious anatomical or histological differences were observed in mutant mice. Besides its significance in tissue morphogenesis, integrin a 2β 1 has been reported to play a major role in hemostasis by mediating platelet adhesion and activation on subendothelial collagen. To define its role in hemostasis, α 2-deficient platelets were analyzed for their capacity to adhere to and aggregate in response to fibrillar or soluble collagen type I. We show that aggregation of α 2-deficient platelets to fibrillar collagen is delayed but not reduced, whereas aggregation to enzymatically digested soluble collagen is abolished. Furthermore, α 2-deficient platelets normally adhere to fibrillar collagen. However, in the presence of an antibody against GPVI (activating platelet collagen receptor), adhesion of α 2-deficient but not wild type platelets is abrogated. These results demonstrate that integrin α 2β 1 significantly contributes to platelet adhesion to (fibrillar) collagen, which is further confirmed by the abolished adhesion of α 2-deficient platelets to soluble collagen. Thus, α 2β 1 plays a supportive rather than an essential role in platelet-collagen interactions. These results are in agreement with the observation that α 2β 1-deficient animals suffer no bleeding anomalies.