Core--Mouse Atherosclerosis and Analysis

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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.