COAGULATION INITIATION IN FACTOR VII DEFICIENT MICE

VII 因子缺陷小鼠的凝血启动

• 批准号: 6628999
• 负责人: ELLIOT David ROSEN
• 金额: $ 12.04万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-02-01 至 2003-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6628999
• 关键词: blood coagulation; blood coagulation disorders; coagulation factor VII; coagulation factor XI; congenital blood disorder; disease /disorder model; embryogenesis; fibrin; gene expression; gene targeting; genetically modified animals; hemostasis; inflammation; laboratory mouse; molecular dynamics; pregnancy circulation; protein structure function; thrombin; thromboplastin; thrombosis

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.

描述：（研究者摘要）本研究的长期目标 是确定凝血因子的体内作用，特别是 因子VII (FVII)。人们普遍认为 FVII 在 血管损伤后开始凝血。该项目的总体目标是 拟议的研究详细检查了凝血的启动和 血管损伤和炎症挑战后的止血反应 FVII 的存在或不存在。 解决该问题的方法是利用最近生成的 FVII- 和 FIX 缺陷小鼠。 FVII(-/-)、FXI(-/-)、FVII(-/-)/FXI(-/-) 和野生型小鼠 血管损伤后进行检查。血栓形成和纤维蛋白 沉积物将受到监测。该战略将揭示以下关键角色： FVII 通过确定哪些过程在缺乏 FVII 的情况下受损。 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对 凝血和血栓形成的起始。 此外，凝血途径中的一些元素已被证明可以 影响胚胎发生。当 FVII 缺陷和 FXI 缺陷小鼠发育时 通常，建议确定是否同时敲除已知的两个 凝血启动途径导致胚胎致死。普通的 FVII/FXI 缺陷双基因缺失的发生可能表明 启动凝血级联反应的替代机制 胚胎发生。 凝血涉及许多正常和病理生理状况 包括止血、血栓形成、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。