GENETIC BASIS OF STROKE IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

该项目的目的是确定中风的遗传基础， 易卒中自发性高血压大鼠（SHRSP）。 SHRSP是 通过Okamoto-Aoki的亚系选择性近亲繁殖而开发 自发性高血压大鼠，以产生模型，其中 中风的易感性是可靠的遗传。 SHRSP和近交系正常血压对照（WKY）的比较， 标准化缺血试验范式，急性中间闭塞 大脑动脉（MCA闭塞），有牵连的能力不足， 桥接MCA和大脑前、后壁的神经桥 动脉作为中风的关键决定因素，虽然基因产物 介导中风素质是未知的。 本提案寻求 为了将这些观察扩展到基因水平， 连锁分析，以确定基因组位点连锁表型 MCA-闭塞性卒中。 利用构建的大鼠基因组图谱， 通过聚合酶链反应分型的简单序列重复，我们将 进行连锁分析，将中风视为定性（存在）和 vs.缺失）和F2中的定量（梗死脑体积）特征 来自SHRSP X WKY杂交的动物。 我们将使用链接标记， 为进一步研究鉴定可能的候选基因， 开发同类菌株，用于研究 兴趣 此外，我们还将研究其他几个表型特征 包括生长和血压的阶段性加速， 与基因组标记连锁的体外维管性状。

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.