TY - JOUR
T1 - β3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival
AU - Hodivala-Dilke, Kairbaan M.
AU - McHugh, Kevin P.
AU - Tsakiris, Dimitrios A.
AU - Rayburn, Helen
AU - Crowley, Denise
AU - Ullman-Culleré, Mollie
AU - Ross, F. Patrick
AU - Coller, Barry S.
AU - Teitelbaum, Steven
AU - Hynes, Richard O.
PY - 1999/1
Y1 - 1999/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0032590042&partnerID=8YFLogxK
U2 - 10.1172/JCI5487
DO - 10.1172/JCI5487
M3 - Article
C2 - 9916135
AN - SCOPUS:0032590042
SN - 0021-9738
VL - 103
SP - 229
EP - 238
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 2
ER -