PLASMA PROTEIN PHENOTYPING OF PROTHROMBOTIC MICE

描述（改编自申请人摘要） 推动这一提议的假设是， 凝血酶形成增加或纤溶酶减少的血浆标志物 在遗传改变的小鼠中的形成/利用可以作为 开发用于小鼠的高输出筛选试验， 血栓形成前表型 确定用于检测 血栓形成前表型对于识别遗传性 具有血栓前状态的转化小鼠。 那些被 基因改变为不表达或过表达蛋白质，所述蛋白质的缺失或 升高水平与血栓形成前状态相关， 有机会检查大量的遗传同质的人口， 受试者存在表征血浆蛋白的特定生化缺陷 血栓形成前动物的表型。 这项建议的具体目的是 如下所示： 具体目标1：具有多种蛋白质的基因敲除或转基因小鼠 与血栓形成前表型相关的缺陷的特征在于 多种血浆测定，证明凝血酶形成增加和/或 降低纤溶酶的形成/利用，以确定哪种测试最 预测血栓形成的表现。 这些研究应确定哪些血浆测定法不是全球性的， 筛选具有血栓形成遗传风险因素的动物。 那些测定 最能预测血栓形成的基因将被选择用于发展成 高输出筛选技术。 此外，这些研究提供的信息， 老鼠也应该有助于了解什么样的实验室研究将是最重要的 预测识别人的血栓形成前表型。这些研究 可作为开发全球测定方法的基础， 人的血栓前状态。（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.)