GENES OF HYPERTENSION AND ASSOCIATED PHENOTYPES IN GENETIC STRAINS OF RATS

大鼠遗传品系中的高血压基因及相关表型

• 批准号: 6110542
• 负责人: Allen W Cowley
• 金额: $ 25.25万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6110542
• 关键词: acetylcholine; angiotensins; animal genetic material tag; dietary sodium; disease /disorder model; familial hypertension; fluorescence microscopy; gene expression; genetic markers; genetic regulation; genetic strain; genome; hyperlipidemia; kidney function; laboratory rat; molecular genetics; norepinephrine; northern blottings; phenotype; polymerase chain reaction; western blottings

The goal of Project 3 is to locate "hypertensive" loci using a large (>300) F2 cross derived from normotensive Brown Norway and Dahl salt- sensitive hypertensive rats. The F2 progeny will be extensively phenotyped after exposure to a high salt diet. In addition to salt- sensitivity, the Dahl S model of hypertension shares many similarities with phenotypic traits associated with hypertension in African Americans including insulin resistance, hyperlipidemia, and rapid development of severe progressive-hypertensive glomerulosclerosis that leads to end- stage renal disease. The F2 progeny will be genotyped using a total genomic search strategy and a candidate gene approach for determination of loci that cosegregate with arterial pressure and hypertension related phenotypes which correspond to those studied in the human populations on Projects 1 and 2 (e.g. vascular reactivity, renal function, and hyperlipidemia). QTLs which cosegregate with blood pressure or hypertension related phenotypes will be converted to homologous regions in the human and then be used to screen our patient populations. Once a region or regions are identified which cosegregate with salt-sensitive hypertension, we propose to enhance the localization of the blood pressure regulatory genes by creating new strains of rats that are identical except for selected regions of a single chromosome (congenic lines). These rats will then enable us to study the physiological mechanisms by which these loci influence blood pressure.

项目 3 的目标是利用大的序列来定位“高血压”基因座。 (>300) F2 杂交源自正常血压布朗挪威和达尔盐- 敏感高血压大鼠。 F2代后代将广泛 暴露于高盐饮食后的表型。除了盐—— 敏感性，高血压的 Dahl S 模型有许多相似之处 具有与非裔美国人高血压相关的表型特征 包括胰岛素抵抗、高脂血症以及快速发展的 严重的进行性高血压肾小球硬化症，导致最终 阶段肾病。 F2 后代将使用总基因型进行基因分型 基因组搜索策略和候选基因确定方法 与动脉压和高血压相关的基因座 表型与在人群中研究的表型相对应 项目 1 和 2（例如血管反应性、肾功能和 高脂血症）。与血压共分离的 QTL 或 高血压相关表型将转化为同源区域 然后用于筛查我们的患者群体。一次 鉴定出与盐敏感性共分离的一个或多个区域 高血压，我们建议加强血液的定位 通过创造新的老鼠品系来压力调节基因 除了单个染色体的选定区域（同类基因）外，其他区域相同 线）。这些老鼠将使我们能够研究生理学 这些基因座影响血压的机制。