Controlling elements of platelet glycoprotein Ib alpha expression.

Our objectives are to define and characterize molecular events of megakaryocytopoiesis and platelet production by analyzing the in vivo expression of platelet glycoprotein (GP) receptors. Our studies target the platelet GP Ib-IX-V complex since the congenital absence of the receptor results in the Bernard-Soulier syndrome, a condition linking the expression of the complex to normal platelet morphogenesis. We have previously described the generation of a transgenic mouse colony expressing the alpha-subunit (GP Ib alpha) of the human platelet GP Ib-IX-V complex. These studies established methodologies to manipulate GP Ib-IX-V on the platelet surface and examine unique aspects of hemostasis, megakaryocytopoiesis, platelet structure and platelet release. Our recent studies have defined the genetic elements supporting the megakaryocytic-expression of GP Ib alpha. These results are defining essential cis-acting elements responsible for the expression of GP Ib alpha and are providing insights into molecular events coinciding with the release of normal platelets into the bloodstream.