TRANSGENIC MODELS OF THROMBIN RECEPTOR FUNCTION

凝血酶受体功能的转基因模型

• 批准号: 2445016
• 负责人: ANDREW J CONNOLLY
• 金额: $ 8.07万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2445016
• 关键词: G protein; alleles; artery stenosis; atherosclerosis; atherosclerotic plaque; biological signal transduction; cell cycle; disease /disorder model; embryonic stem cell; gene mutation; genetic recombination; genetically modified animals; hemostasis; inflammation; laboratory mouse; model design /development; phenotype; platelet activation; receptor; thrombin; thrombosis; tissue /cell culture; vascular endothelium; vascular smooth muscle; wound healing

Thrombin is a multifunctional serine protease generated at sites of vascular injury. Its potent in vitro actions on platelets, leukocytes, vascular and mesenchymal cells suggest that thrombin may mediate not only hemostatic and thrombotic, but also inflammatory and proliferative responses in vivo. The thrombin receptor that was cloned and characterized by Dr. Coughlin appears to mediate many of these cellular events and provides a new tool for defining the relative importance of thrombin in various in vivo processes. We will address the hypotheses that thrombin receptor activation plays an important role in hemostasis, thrombosis, arterial restenosis, atherogenesis, and wound healing. The most expeditious and definitive approach is to introduce inactivating and activating mutations of thrombin receptor into mice by using embryonic stem cells and gene targeting by homologous recombination.

凝血酶是一种多功能丝氨酸蛋白酶，在 血管损伤。 它在血小板，白细胞，有效的体外作用， 血管和间质细胞表明凝血酶不仅可以介导 止血和血栓形成，但也炎症和增生 体内反应。 克隆的凝血酶受体和 Coughlin博士的特征似乎介导了其中许多细胞 事件并提供了一种新工具来定义 凝血酶在各种体内过程中。 我们将解决假设 该凝血酶受体激活在止血中起重要作用， 血栓形成，动脉再狭窄，动脉粥样硬化和伤口愈合。 这 最迅速，最确定的方法是引入失活和 通过使用胚胎将凝血酶受体的突变激活到小鼠中 干细胞和基因通过同源重组靶向。