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

Kairbaan M. Hodivala-Dilke, Kevin P. McHugh, Dimitrios A. Tsakiris, Helen Rayburn, Denise Crowley, Mollie Ullman-Culleré, F. Patrick Ross, Barry S. Coller, Steven Teitelbaum, Richard O. Hynes

Research output: Contribution to journalArticlepeer-review

673 Scopus citations

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.

Original languageEnglish
Pages (from-to)229-238
Number of pages10
JournalJournal of Clinical Investigation
Volume103
Issue number2
DOIs
StatePublished - Jan 1999

Fingerprint

Dive into the research topics of 'β3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival'. Together they form a unique fingerprint.

Cite this