[en] Rasa3 is a GTPase activating protein of the GAP1 family whiwh target Ras and Rap1. Rasa3 catalytic inactivation in mice (Rasa3-/-) results in early embryonic lethality. Here, we show that irradiated nude mice reconstituted with Rasa3-/- hematopietic cells (SCID-Rasa3-/-) present a lethal syndrome characterized by severe defects during megakaryopoiesis, thrombocytopenia and a predistosition to preleukemia. These Rasa3-/- megakaryocites (MKs) have an increased active Rap1 and constitutive integrin activation, recapitulated in Rasa"+/- platelets, that leed to defects in migration, adhesion and differentiation into proplatelet forming megakaryocytes.
