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

TLDR

β3 integrins play roles in platelet aggregation, thrombosis, implantation, placentation, angiogenesis, bone remodeling, and tumor progression, and mutations in the αIIb or β3 subunits cause the bleeding disorder Glanzmann thrombasthenia. The authors generated a β3‑null mouse strain to model Glanzmann thrombasthenia and to investigate β3 integrin functions in hemostasis, thrombosis, and other suggested roles. They produced β3‑null mice by knocking out the β3 integrin gene in a mouse strain. The β3‑null mice are viable and fertile, display classic Glanzmann thrombasthenia phenotypes, have placental defects leading to fetal loss, suffer postnatal hemorrhage causing anemia and reduced survival, and show that retinal neovascularization after birth is β3‑integrin–independent.

Abstract

β3 integrins have been implicated in a wide variety of functions, including platelet aggregation and thrombosis (αIIbβ3) and implantation, placentation, angiogenesis, bone remodeling, and tumor progression (αvβ3). The human bleeding disorder Glanzmann thrombasthenia (GT) can result from defects in the genes for either the αIIb or the β3 subunit. In order to develop a mouse model of this disease and to further studies of hemostasis, thrombosis, and other suggested roles of β3 integrins, we have generated a strain of β3-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 β3 integrins and we report that postnatal neovascularization of the retina appears to be β3-integrin–independent, contrary to expectations from inhibition experiments.