Core--Mouse Atherosclerosis and Analysis

动脉粥样硬化的小鼠模型提供了一个机会，以检查特定基因在动脉粥样硬化中的作用。 病变的发生和进展，但来自不同已发表研究的数据往往很难 compare.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，以及测试仅限于单一小鼠模型。为了解决这些问题，核心A 将使用相同的协议为所有的小鼠研究，利用饮食模拟Th1炎症 在人类疾病中观察到的反应，分析多个时间点， 损伤发展，并分析所有小鼠的3个损伤形成位点。它将集中 基因敲除小鼠的产生和繁殖，并将使用 这些动物。核心实验室最近还开发了一种巨噬细胞特异性逆转录病毒 允许造血干细胞的有效转导从而导致基因表达的载体 在体内损伤巨噬细胞中。本PPG中的所有项目都将利用这些方法来干扰 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、协调和规范所有人的牺牲， 项目研究动物，准备和盲组织进行分析，提供组织学染色和所有 定量分析方法。使用相同方案的组合分析将允许直接 不同炎症基因产物干扰的影响比较，包括 参与巨噬细胞募集和激活调节的炎性基因， 生存之路。

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.