COAGULATION INITIATION IN FACTOR VII DEFICIENT MICE

描述：(研究人员摘要)这项研究的长期目标 是为了确定凝血因子在体内的作用，特别是凝血因子 因子VII(Fvii)。人们普遍认为，Fvii在 血管损伤后开始凝血。该计划的总体目标 建议的研究是详细地检查凝聚的启动和 血管损伤和炎性刺激后的止血反应 存在或不存在FVII。 解决这个问题的方法是利用最近生成的FVII-和 修复缺陷的小鼠。FVII(-/-)、FXI(-/-)、FVII(-/-)/FXI(-/-)和野生型小鼠 将在血管损伤后进行检查。血栓形成与纤维蛋白 将对沉积情况进行监测。这一战略将揭示 FVII通过确定哪些过程在没有FVII的情况下受到损害。 此外，通过从基因上阻止FVII启动的凝血，它将 可能确定FXI是否以及在多大程度上对 开始凝血和血栓形成。 此外，凝血途径中的几个元素已被证明 影响胚胎发育。而FVII基因缺陷和FXI基因缺陷的小鼠 通常，建议确定是否同时敲除这两个已知的 凝血启动途径导致胚胎死亡。正常 FVII/FXI缺陷双基因缺失的发生可能提示 启动凝血级联反应的替代机制 胚胎发生。 凝血与许多正常和病理生理状态有关。 包括止血、血栓、炎症、动脉粥样硬化和癌症。 拟议的研究将有助于我们对元素的理解 有助于体内凝血的启动。

DESCRIPTION: (Investigator's abstract) The long-term objective of this research is to determine the in vivo role of coagulation factors, specifically that of Factor VII (FVII). FVII is generally accepted to play a key role in the initiation of coagulation following vascular injury. The overall goal of the proposed research is examine in detail the initiation of coagulation and hemostatic response after vascular injury and inflammatory challenge in the presence or absence of FVII. The approach to the problem is to utilize recently generated FVII- and FIX-deficient mice. FVII(-/-), FXI(-/-), FVII(-/-)/FXI(-/-) and wild-type mice will be examined after vascular injury. Thrombus formation and fibrin deposition will be monitored. This strategy will reveal the critical roles of FVII by identifying which processes are impaired in the absence of FVII. Furthermore, by genetically blocking FVII-initiated coagulation, it will be possible to identify whether and to what extent FXI contributes to the initiation of coagulation and thrombus formation. In addition, several elements in the coagulation pathway have been shown to affect embryogenesis. While FVII-deficient and FXI-deficient mice develop normally, it is proposed to determine if simultaneous knockout of both known coagulation initiating pathways result in embryonic lethality. Normal development of FVII/FXI-deficient double gene deletions might suggest alternative mechanisms to initiate the coagulation cascade during embryogenesis. Coagulation is involved in many normal and pathophysiological conditions including hemostasis, thrombosis, inflammation, atherosclerosis, and cancer. The proposed research will contribute to our understanding of elements contributing to coagulation initiation in vivo.