GENETIC BASIS OF STROKE IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

这个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 冈本青木亚种选育而成 建立一种自发性高血压大鼠模型 中风的易感性是可靠的遗传遗传。 SHRSP与近交系正常血压对照(WKY)的比较 标准化的缺血测试范式，急性中段闭塞 大脑动脉(大脑中动脉闭塞)，已牵涉容量不足 大脑中动脉与大脑前、后部的吻合 动脉作为中风的关键决定因素，尽管基因产物 调节中风素质的因素尚不清楚。本提案旨在 通过使用基因将这些观察扩展到遗传水平 利用连锁分析鉴定与表型相关的基因组位点 大脑中动脉-阻塞性卒中。使用构建的老鼠基因组图 通过聚合酶链式反应分型的简单序列重复，我们将 执行连锁分析，将中风视为定性(存在) 与缺失相比)和数量(脑梗塞体积)性状 来自SHRSP×WKY杂交的动物。我们将使用链接标记来 确定可能的候选基因以供进一步研究并指导 用于研究沙门氏菌基因组基因座的同源菌株的建立 利息。此外，我们还将研究其他几种表型特征。 SHRSP包括生长和血压的阶段性加速以及 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.