AOP2 AND ATHEROSCLEROSIS RESISTANCE AND MICE

AOP2 和动脉粥样硬化抵抗与小鼠

• 批准号: 2767602
• 负责人: Shelley A Phelan
• 金额: $ 3.17万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2767602
• 关键词: animal breeding; atherosclerosis; disease /disorder model; gene expression; genetic promoter element; genetic susceptibility; genetically modified animals; in situ hybridization; laboratory mouse; model design /development; molecular cloning; nucleic acid sequence; oxidative stress; polymerase chain reaction; tissue /cell culture

DESCRIPTION Previous studies from our laboratory have demonstrated that susceptibility to atherosclerosis differs significantly between inbred strains of mice, suggesting a strong genetic component to the disease. Athl is a quantitative trait locus that we found to be associated with decreased plasma HDL-cholesterol levels and increased atherosclerotic lesion formation in susceptible strains of mice when fed a high fat diet. We have recently identified a Athl candidate gene, Aop2, which is a member of the thiol-specific antioxidant family. We believe Aop2 mediates protection from atherosclerosis based on its chromosomal co-localization with Athl, mRNA induction by high fat diet, amino acid and expression differences between resistant and susceptible strains, and the proposed role of LDL oxidation in the pathogenesis of atherosclerosis. I propose three specific aims toward the characterization of AOP2 in atherosclerosis resistance: 1) obtain definitive proof that AOP2 confers resistance to atherosclerosis by transgenic rescue; 2) characterize expression of AOP2 in the arterial wall; and 3) determine the molecular basis for the regulatory differences observed between atherosclerosis resistant and susceptible strains.

描述 我们实验室以前的研究已经证明了易感性 对动脉粥样硬化的影响在近交系小鼠之间存在显著差异， 这表明这种疾病有很强的遗传成分。THL是一种 我们发现与减少相关的数量性状基因座 血浆高密度脂蛋白-胆固醇水平与动脉粥样硬化病变增加 当喂食高脂肪食物时，易感品系的小鼠形成。我们有 最近发现了一个athl候选基因aop2，它是 特定于硫醇的抗氧化剂家族。我们相信Aop2可以调节保护 基于其与ATL的染色体共定位而导致的动脉硬化， 高脂饮食、氨基酸对mRNA的诱导及其表达差异 耐药株和敏感株之间的关系以及低密度脂蛋白的作用 氧化在动脉粥样硬化发病机制中的作用。我提出三个具体的建议 旨在研究AOP2在动脉粥样硬化抵抗中的作用：1) 获得AOP2通过以下方式抵抗动脉粥样硬化的确凿证据 2)AOP2在动脉中的表达特征 WALL；3)确定调控差异的分子基础 在动脉粥样硬化抵抗株和易感株之间观察。