COAGULATION INITIATION IN FACTOR VII DEFICIENT MICE

描述：（研究者摘要）本研究的长期目标 是为了确定凝血因子在体内的作用，特别是 因子VII（FVII）。FVII通常被认为在 血管损伤后开始凝血。的总体目标 建议的研究是详细检查混凝的启动， 血管损伤和炎症激发后的止血反应 是否存在FVII。 解决这个问题的方法是利用最近产生的FVII-和 FIX缺陷小鼠。FVII（-/-）、FXI（-/-）、FVII（-/-）/FXI（-/-）和野生型小鼠 将在血管损伤后进行检查。血栓形成和纤维蛋白 将监测沉积。这一战略将揭示关键作用， 通过识别在没有FVII的情况下哪些流程受到损害来评估FVII。 此外，通过基因阻断FVII引发的凝血， 可以确定FXI是否以及在多大程度上有助于 引发凝血和血栓形成。 此外，凝血途径中的几个要素已被证明， 影响胚胎发生。当FVII缺陷和FXI缺陷小鼠发育成 通常，建议确定是否同时敲除两个已知的 凝血起始途径导致胚胎死亡。正常 FVII/FXI缺陷型双基因缺失的发生可能提示 启动凝血级联的替代机制， 胚胎发生 凝血参与许多正常和病理生理条件 包括止血、血栓形成、炎症、动脉粥样硬化和癌症。 建议的研究将有助于我们了解元素 有助于体内凝固起始。

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.