GENETIC BASIS OF STROKE IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

易发生中风的自发性高血压大鼠中风的遗传基础

• 批准号: 6241574
• 负责人: ALAN B WEDER
• 金额: $ 15.7万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6241574
• 关键词: disease /disorder model; gene expression; genetic markers; genetic strain; genome; hypertension; inbreeding; laboratory rat; linkage mapping; model design /development; northern blottings; nutrition related tag; phenotype; polymerase chain reaction; stroke; western blottings

The aim of this project is to define the genetic basis of stroke in the stroke-prone spontaneously hypertensive rat (SHRSP). SHRSP were developed by selective inbreeding of substrains of the Okamoto-Aoki spontaneously hypertensive rat to produce a model in which a predisposition to stroke is reliably genetically transmitted. Comparisons of SHRSP and inbred normotensive controls (WKY) using a standardized ischemic test paradigm, acute occlusion of the middle cerebral artery (MCA-occlusion), have implicated inadequate capacity of the anastomoses bridging the MCA and the anterior and posterior cerebral arteries as the critical determinant of stroke, although the gene product mediating the stroke diathesis is unknown. The present proposal seeks to extend these observations to the genetic level by using genetic linkage analysis to identify genomic sites linked to the phenotype of MCA-occlusion stroke. Using a map of the rat genome constructed from simple sequence repeats typed by the polymerase chain reaction, we will perform linkage analyses treating stroke as both a qualitative (presence vs. absence) and a quantitative (volume of infarcted brain) trait in F2 animals derived from SHRSP X WKY crosses. We will use linked markers to identify possible candidate genes for further study as well as to direct development of congenic strains for study of the genomic locus of interest. In addition, we will examine several other phenotype features of SHRSP, including phasic accelerations in growth and blood pressure and in vitro vascular characters for linkage with genomic markers.

该项目的目的是定义中风的遗传基础 自发性高血压大鼠（SHRSP）。 Shrsp是 通过选择性近亲繁殖的冈本-Aoki的基质开发 自发性高血压大鼠产生一个模型 中风的易感性是可靠的基因传播。 使用A的SHRSP和近交性近交性控制（WKY）的比较 标准化缺血测试范式，中间的急性阻塞 脑动脉（MCA-氯化）牵涉到能力不足的 吻合桥接MCA和前后大脑 尽管基因产物，但动脉作为中风的关键决定因素 介导卒中素质是未知的。 目前的提议寻求 通过使用遗传来将这些观察结果扩展到遗传水平 链接分析以识别与表型相关的基因组位点 MCA-重纹性中风。 使用从 由聚合酶链反应键入的简单序列重复，我们将 进行连锁分析将中风视为定性（存在） 与缺席）和F2中的定量（梗塞大脑的体积）特征 源自SHRSP X WKY十字架的动物。 我们将使用链接标记来 确定可能的候选基因进行进一步研究以及指导 生长菌株的开发用于研究的基因组基因座 兴趣。 此外，我们将检查其他几个表型特征 SHRSP，包括生长和血压的阶段加速度以及 与基因组标记联系的体外血管特征。