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.)
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