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 α2β1 develop normally, are fertile, and like their systemic α2β1 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 α2β1. At the same time, we observed a significant reduction in mean platelet volume, which is consistent with the reported role of α2β1 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 α2 integrin in selected cell types.
Roon Research Center for Arteriosclerosis and Thrombosis, The Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA.
David
D
Habart
Yann
Y
Cheli
Diane J
DJ
Nugent
Zaverio M
ZM
Ruggeri
Thomas J
TJ
Kunicki
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002448:Cell Adhesion; D024042:Collagen Type I / Q000378:metabolism; D017931:DNA Primers; D055786:Gene Knockout Techniques; D038982:Integrin alpha2beta1 / Q000235:genetics / Q000502:physiology*; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D010976:Platelet Count; D016133:Polymerase Chain Reaction
D024042:Collagen Type I; D017931:DNA Primers; D038982:Integrin alpha2beta1