β3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival

beta 3 integrins have been implicated in a wide variety of functions, including platelet aggregation and thrombosis (alpha IIb beta 3) and implantation, placentation, angiogenesis, bone remodeling, and tumor progression (alpha v beta 3). The human bleeding disorder Glanzmann thrombasthenia (GT) can result from defects in the genes for either the alpha IIb or the beta 3 subunit. In order to develop a mouse model of this disease and to further studies of hemostasis, thrombosis, and other suggested roles of beta 3 integrins, we have generated a strain of beta 3-null mice. The mice are viable and fertile, and show all the cardinal features of GT (defects in platelet aggregation and clot retraction, prolonged bleeding times, and cutaneous and gastrointestinal bleeding). Implantation appears to be unaffected, but placental defects do occur and lead to fetal mortality. Postnatal hemorrhage leads to anemia and reduced survival. These mice will allow analyses of the other suggested functions of beta 3 integrins and we report that postnatal neovascularization of the retina appears to be beta 3-integrin-independent, contrary to expectations from inhibition experiments.