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β3-integrin–deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival
Kairbaan M. Hodivala-Dilke, … , Steven Teitelbaum, Richard O. Hynes
Kairbaan M. Hodivala-Dilke, … , Steven Teitelbaum, Richard O. Hynes
Published January 15, 1999
Citation Information: J Clin Invest. 1999;103(2):229-238. https://doi.org/10.1172/JCI5487.
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Article

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

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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.

Authors

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

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Figure 3

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Survival of β3-null mice is compromised. Uteri from typical wild-type (a...
Survival of β3-null mice is compromised. Uteri from typical wild-type (a) and β3-null (b) females that had been bred to β3-null or wild-type males, respectively. Dark patches in (b) indicate bleeding in β3-null uterus. (c and d) Heterozygous E16 embryos in utero, in wild-type (c) or β3-null (d) mothers. Some pups die in β3-null mothers in utero, appearing pale, small and associated with a pale placenta (arrow). (e, f and h) H&E stained sections of placentae from β3-null females mated with wild-type males. H&E stained section of placenta from wild-type female mated with a β3-null male (g). Arrowhead indicates severe hemorrhage observed within the labyrinth (e) and under the Reichert's membrane (f). (g) Labyrinth of wild-type placenta; (h) Labyrinth of β3-null placenta where cell layers appear thick; this occurs in ∼25% of β3-null placentae. (i and j) E16 embryos, wild-type (i) and β3-null (j). Note hemorrhage in β3-null muzzle. Arrow indicates hemorrhage in the skin. (k, l, m, and n) After birth, some β3-null mice suffer hemorrhage in the skin. Petechiae around the mouth of a 1-day-old β3-null pup (k) and H&E-stained section of this region indicating bleeding under the epidermis (l). Purpura on the forelimb of a 1-day-old β3-null pup (m) and H&E-stained section of this region indicating bleeding within the dermis (n). (o and p) Gut from newborn pups. Wild-type (o) and β3-null pup with acute GI hemorrhage (p). Bar (e), 400 μm (f), 50 μm, and (g), 70 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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