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Influence of the genetic background on platelet function, microparticle and thrombin generation in the common laboratory mouse.

机译:遗传背景对普通实验小鼠的血小板功能,微粒和凝血酶生成的影响。

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Genetic background has been shown to affect phenotype in transgenic mice with hemostatic defects. We present comparative data on various platelet function tests, as well as on microparticle and thrombin generation capacity in three mouse strains most commonly used in transgenic applications. Normal, inbred 129Sv (n = 24), C57BL/6 (n = 14) and BALB/c (n = 22) mice were used. BALB/c mice showed statistically significantly longer tail-bleeding times (158 +/- 42 s, P<0.02) than 129Sv (113 +/- 37) and C57BL/6 (122 +/- 29) and paradoxically increased velocity of platelet aggregation (P<0.01) with ADP, collagen, ionophore and thrombin. ATP-release did not differ between strains, it was weakest with ADP and strongest with thrombin. 129Sv platelets were less responsive to thrombin. Generation of platelet microparticles did not differ between strains either and could efficiently be inhibited by EDTA but not by aspirin or alprostadil. Two anti-GPIIIa monoclonal antibodies did not inhibit microparticles either, although they could block aggregation. Thrombin generation was equivalent in C57BL/6 and BALB/c, but slower in 129Sv. Interestingly, the reaction in all strains was immediate and different from the human model in that no lag-phase was seen after triggering. In summary these mouse strains show similar patterns of ex vivo platelet aggregation, bleeding times as well as microparticle and thrombin generation. Subtle differences were found, which should be taken into consideration when interpreting data from wild-type or transgenic models.
机译:已经证明遗传背景会影响具有止血缺陷的转基因小鼠的表型。我们提供了各种血小板功能测试的比较数据,以及在转基因应用中最常用的三种小鼠品系中的微粒和凝血酶生成能力。使用了正常的近交129Sv(n = 24),C57BL / 6(n = 14)和BALB / c(n = 22)小鼠。 BALB / c小鼠的尾巴出血时间(158 +/- 42 s,P <0.02)在统计学上比129Sv(113 +/- 37)和C57BL / 6(122 +/- 29)长得多,并且自相矛盾的是血小板速度增加与ADP,胶原蛋白,离子载体和凝血酶的聚集(P <0.01)。菌株之间的ATP释放没有差异,ADP最弱,凝血酶最强。 129Sv血小板对凝血酶的反应较弱。菌株之间的血小板微粒的产生也没有区别,并且可以被EDTA有效抑制,但不能被阿司匹林或前列地尔抑制。两种抗GPIIIa单克隆抗体也不能抑制微粒,尽管它们可以阻止聚集。凝血酶的生成在C57BL / 6和BALB / c中是等效的,但在129Sv中则较慢。有趣的是,所有菌株中的反应都是即时的,并且与人类模型不同,因为在触发后没有看到滞后阶段。总之,这些小鼠品系显示出相似的离体血小板聚集,出血时间以及微粒和凝血酶生成模式。发现了细微的差异,在解释来自野生型或转基因模型的数据时应考虑在内。

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