PLASMA PROTEIN PHENOTYPING OF PROTHROMBOTIC MICE

描述(改编自申请人的摘要) 推动这一提议假设是各种不同的特征 凝血酶形成增加或纤溶酶降低的血浆标志物 转基因小鼠的形成/利用可能成为 小鼠血吸虫病高产量筛选试验(S)的建立 血栓前表型。确定有用的化验方法(S)以检测 血栓前表型对遗传性高血压的识别很重要 转化成血栓前状态的小鼠。小鼠已经被 不表达或过度表达其缺失或缺失的蛋白质 升高的水平与血栓前状态相关，提供了 有机会检查大量遗传同质的人群 特定生化缺陷的受试者，这些缺陷是血浆蛋白的特征 血栓前动物的表型。这项建议的具体目的是 详情如下： 具体目标1：用多种蛋白质敲除或转基因小鼠 与血栓前表型相关的缺陷将表现为 显示凝血酶形成和/或增加的各种血浆检测 纤溶酶形成/利用减少，以确定哪一项测试(S)最多 对血栓形成的表现有预测性。 这些研究应该确定哪些血浆检测不是全球性的。 筛选具有血栓形成遗传风险因素的动物。那些化验 最能预测血栓形成的将被选为 高产筛选技术。此外，从这些研究中获得的信息 老鼠也应该是有用的，以了解什么是最重要的实验室研究 预测识别男性血栓前表型。这些研究 可以作为发展全球化验(S)的基础，以预测 人类的血栓前状态。(摘要结束。)

DESCRIPTION (Adapted from the applicant's abstract) The hypothesis that drives this proposal is that characterization of various plasma markers for increased thrombin formation or decreased plasmin formation/utilization in genetically altered mice may serve as the basis for the development of a high output screening assay(s) for mice with prothrombotic phenotypes. Determining a useful assay(s) to detect the prothrombotic phenotype is important for the recognition of genetically transformed mice that have a prothrombotic state. Mice that have been genetically altered not to express or over express a protein whose absence or increase levels is associated with a prothrombotic state provide an opportunity to examine a large number of genetically homogenous population of subjects for specific biochemical defects that characterize the plasma protein phenotype of the prothrombotic animal. The specific aim of this proposal is as follows: Specific Aim 1: Knockout or transgenic mice with a wide variety of protein defects associated with the prothrombotic phenotype will be characterized by a variety of plasma assays that demonstrate increased thrombin formation and/or decreased plasmin formation/utilization to determine which test(s) is most predictive for the presentation of thrombosis. These studies should determine which plasma assays are mot global for screening animals with genetic risk factors for thrombosis. Those assays which are most predictive of thrombosis will be selected for development into high output screening techniques. Further, information from these studies on mice should also be useful to understand what laboratory studies will be most predictive to recognize the prothrombotic phenotype in man. These studies could serve as a basis for the development of a global assay(s) to predict the prothrombotic state in man. (End of Abstract.)