Conditional Knockout of Integrin α2β1 in Murine Megakaryocytes Leads to Reduced Mean Platelet Volume

We have engineered a transgenic mouse on a C57BL/6 background that bears a floxed Itga2 gene. The crossing of this mouse strain to transgenic mice expressing Cre recombinase driven by the megakaryocyte (MK)-specific Pf4 promoter permits the conditional knockout of Itga2 in the MK/platelet lineage. Mice lacking MK alpha 2 beta 1 develop normally, are fertile, and like their systemic alpha 2 beta 1 knockout counterparts, exhibit defective adhesion to and aggregation induced by soluble type I collagen and a delayed onset to low dose fibrillar collagen-induced aggregation, results consistent with blockade or loss of platelet alpha 2 beta 1. At the same time, we observed a significant reduction in mean platelet volume, which is consistent with the reported role of alpha 2 beta 1 in MK maturation and proplatelet formation in vivo. This transgenic mouse strain bearing a floxed Itga2 gene will prove valuable to distinguish in vivo the temporal and spatial contributions of alpha 2 integrin in selected cell types.