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Dissection of blood pressure QTL using substrains of the spontaneously hypertensive rats ans congenic strains

自发性高血压大鼠亚系和同类系的血压QTL解析

基本信息

批准号：
16300136
负责人：
NABIKA Toru
金额：
$ 9.73万
依托单位：
Shimane University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16300136/
关键词：
essential hypertension Spontaneously Hypertensive Rats quantitative trait locus 本態性高血圧

项目摘要

Previous reports of our laboratory showed that a quantitative trait locus (QTL) for blood pressure is located on rat chromosome 1.The evaluation of a congenic strain targeting this QTL indicated that the responsible gene(s) was in 80Mbp region. This region was still quite large and therefore it should be cut down into smaller regions to identify the responsible genes. In the process of developing the spontaneously hypertensive rats (SHR), several substrains of SHR and the stroke-prone SHR (SHRSP) have been developed and maintained for more than 20 years. As they are expected to share the same ‘hypertension' genes with each other, we hypothesized that the choromosomal fragment around the ‘hypertension' genes harbored a cluster of SSR markers that are polymorphic between SHR substrains and Wistar-Kyoto rat (WKY) substrains ; one allele of such an SSR was commonly shared in the substrains of SHR while another was observed in WKY substrains.In this study, we therefore genotyped 270 SSR mar … More kers distributed densely in the chromosome-1 QTL region. Results indicated that two small fragments (3Mbp) in the region harbored clusters of SSR markers polymorphic between WKY substrains and SHR/SHRSP substrains. These regions are potential candidates having the genes responsible for the blood pressure difference between SHR (and SHRSP) and WKY. We found another fragment with 7Mbp that harbors SSR markers polymorphic between SHRSP substrains and SHR/WKY substrains. This region may account for the difference of blood pressure between SHR and SHRSP, which was indicated by a QTL analysis between SHRSP and SHR as well. We additionally evaluated blood pressure in SHR and SHRSP substrains with the telemetry system. The result indicated that all of SHR/SHRSP substrains had higher blood pressure than did WKY. However, difference of blood pressure among the substrains was significant as well ; some substrains had greater blood pressure than others. According to the genotyping result, no regions in the QTL could account for this inter-substrain difference of blood pressure. QTLs outside of the one on chromosome-1 may be responsible for this difference. Less

本实验室的研究表明，在大鼠1号染色体上存在一个与血压相关的数量性状位点（QTL）。这一区域仍然很大，因此应该将其切割成更小的区域，以确定负责的基因。在自发性高血压大鼠（SHR）的发展过程中，SHR的几个亚系和易卒中SHR（SHRSP）已经发展并维持了20多年。由于它们可能具有相同的高血压基因，我们推测高血压基因的染色体片段上存在一簇SSR标记，这些标记在SHR和WKY之间具有多态性;该SSR的一个等位基因在SHR亚系中普遍存在，而在WKY亚系中观察到另一个等位基因。因此，我们对270个SSR标记进行了基因分型， ...更多信息 kers密集分布在第1染色体QTL区域。结果表明，在WKY亚系和SHR/SHRSP亚系之间，有两个3 Mbp的小片段具有多态性。这些区域是潜在的候选者，具有负责SHR（和SHRSP）和WKY之间血压差异的基因。另外还发现了一个7 Mbp的片段，该片段在SHR/WKY和SHRSP两个亚系间具有多态性。该区域可能是SHR和SHRSP之间血压差异的原因之一，SHRSP和SHR之间的QTL分析也表明了这一点。此外，我们评估血压在SHR和SHRSP亚株与遥测系统。结果表明，SHR/SHRSP各亚系的血压均高于WKY。但各亚株之间的血压差异也很大，有些亚株的血压比其他亚株高。根据基因分型结果，QTL中没有区域可以解释这种亚系间血压差异。1号染色体上的QTL以外的QTL可能是造成这种差异的原因。少