Core--Mouse Atherosclerosis and Analysis

核心--小鼠动脉粥样硬化及分析

• 批准号: 7140041
• 负责人: Elaine W Raines
• 金额: $ 48.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140041
• 关键词: atherosclerosis; atherosclerotic plaque; biomedical facility; bone marrow transplantation; cell type; disease /disorder model; extracellular; genetically modified animals; inflammation; intracellular; laboratory mouse; lead; lipids; macrophage; smooth muscle

Mouse models of atherosclerosis provide an opportunity to examine the role of particular genes in lesion initiation and progression, but the data from different published studies are often difficult to compare. This is due to the use of different diets, analysis times (primarily very short times), sites of analysis, and the limitation of testing to a single mouse model. To address these problems, Core A will use the same protocols for all mouse studies, utilize a diet the mimics the Th1 inflammatory response observed in human disease, analyze multiple time points including very late stages of lesion development, and analyze 3 sites of lesion formation for all mice. It will centralize the generation and breeding of gene-knockout mice, and will perform bone-marrow transplants using these animals. The core laboratory has also recently developed a macrophage-specific retroviral vector that allows efficient transduction of hematopoietic stems cells that leads to gene expression in lesion macrophages in vivo. All of the projects in this PPG will utilize these approaches to perturb inflammatory genes and ask how these changes alter the initiation and progression of atherosclerotic lesions. The Core will also facilitate, coordinate and standardize sacrifice of all project study animals, prepare and blind tissue for analysis, provide histological stains and all quantitative methods of analysis. The combined analyses using identical protocols will allow direct comparison of the effects of perturbation of different inflammatory gene products, including inflammatory genes involved in the regulation of macrophage recruitment and activation and survival pathways.

动脉粥样硬化小鼠模型提供了研究特定基因在动脉粥样硬化中的作用的机会 病变的发生和进展，但来自不同已发表研究的数据往往难以确定 比较。这是由于使用不同的饮食、分析时间（主要是非常短的时间）、分析部位 分析以及对单个小鼠模型进行测试的局限性。为了解决这些问题，核心A 将对所有小鼠研究使用相同的方案，使用模仿 Th1 炎症的饮食 在人类疾病中观察到的反应，分析多个时间点，包括非常晚期的阶段 病变发展，并分析所有小鼠的 3 个病变形成部位。它将集中 产生和培育基因敲除小鼠，并将使用 这些动物。核心实验室最近还开发了巨噬细胞特异性逆转录病毒 允许有效转导造血干细胞从而导致基因表达的载体 体内病变巨噬细胞。该 PPG 中的所有项目都将利用这些方法来扰乱 炎症基因并询问这些变化如何改变炎症的发生和进展 动脉粥样硬化病变。核心还将促进、协调和标准化所有牺牲 项目研究动物，准备和盲化组织进行分析，提供组织学染色和所有 定量分析方法。使用相同协议的组合分析将允许直接 比较不同炎症基因产物的扰动效果，包括 炎症基因参与巨噬细胞募集和激活的调节 生存途径。