β3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival
β3-integrin-deficient mice are a model for Glanzmann thrombasthenia showing placental defects and reduced survival
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DOI：
10.1172/jci5487
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发表时间：
1999-01-01
影响因子：
15.9
通讯作者：
Hynes, RO
中科院分区：
文献类型：
--
作者：
Hodivala-Dilke, KM;McHugh, KP;Hynes, RO
β3整合素涉及多种功能，包括血小板聚集和血栓形成（αIIbβ3）以及着床、胎盘形成、血管生成、骨重塑和肿瘤进展（αvβ3）。人类出血性疾病——血小板无力症（GT）可由αIIb或β3亚基的基因缺陷引起。为了建立这种疾病的小鼠模型，并进一步研究止血、血栓形成以及β3整合素的其他可能作用，我们培育了一种β3基因缺失的小鼠品系。这些小鼠能够存活且具有生育能力，并表现出血小板无力症的所有主要特征（血小板聚集和血块收缩缺陷、出血时间延长以及皮肤和胃肠道出血）。着床似乎未受影响，但确实存在胎盘缺陷并导致胎儿死亡。出生后的出血导致贫血和存活率降低。这些小鼠将有助于分析β3整合素的其他可能功能，并且我们报告，与抑制实验的预期相反，视网膜出生后的新生血管形成似乎不依赖于β3整合素。
beta 3 integrins have been implicated in a wide variety of functions, including platelet aggregation and thrombosis (alpha IIb beta 3) and implantation, placentation, angiogenesis, bone remodeling, and tumor progression (alpha 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 subunit. In order to develop a mouse model of this disease and to further studies of hemostasis, thrombosis, and other suggested roles of beta 3 integrins, 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 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 beta 3 integrins and we report that postnatal neovascularization of the retina appears to be beta 3-integrin-independent, contrary to expectations from inhibition experiments.