beta 3-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, inclu ding platelet aggregation and thrombosis (alpha IIb beta 3) and implantatio n, placentation, angiogenesis, bone remodeling, and tumor progression (alph a 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 sub unit. In order to develop a mouse model of this disease and to further stud ies of hemostasis, thrombosis, and other suggested roles of beta 3 integrin s, 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 aggr egation and clot retraction, prolonged bleeding times, and cutaneous and ga strointestinal bleeding). Implantation appears to be unaffected, but placen tal defects do occur and lead to fetal mortality. Postnatal hemorrhage lead s to anemia and reduced survival. These mice will allow analyses of the oth er suggested functions of beta 3 integrins and we report that postnatal neo vascularization of the retina appears to be beta 3-integrin-independent, co ntrary to expectations from inhibition experiments.