Pathophysiological・Biochemical Cooperative Studies by Linkage Analysis on Hypertension Genes in SHR

SHR高血压基因连锁分析的病理生理生化协同研究

基本信息

批准号：
07308076
负责人：
YAMORI Yukio
金额：
$ 1.92万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07308076/
关键词：
Hypertension Stroke Gene Linkage analysis Renal function Cardiac hypertrophy Endocrine system Intracellular message transduction SHR SHRSP 食塩血管内皮 DNA 交雑実験

项目摘要

Linkage analyzes of genes related to hypertension and stroke were cooperatively carried out in the F_2 generation obtained by cross breeding of spontaneously hypertensive rats (SHR) or stroke-prone SHR (SHRSP) with their control normotensive Wistar-Kyoto (WKY) rats which had been established all as the reference strains such as SHR/Izm, SHRSP/Izm and WKY/Izm. These sets of F_2 rats were carefully observed for the development of hypertension, stroke and other phenotypes related to these pathophysiological conditions, and the following results of the linkage analyzes were obtained.1) Strong linkage with systolic blood pressure (SBP) was detected at 3 loci on Chromosome (Chr.) 1 (DIMIT2), Chr.3 (D3Mgh16) and Chr.4 (TRY1), and less strong linkage was observed at 2 loci on Chr.9 and 10. Blood pressure distribution in the F_2 rats was explained mostly by the genetic influence of these 5 loci.2) On Chr.1 the major gene related to SBP located within 35cM from gene loci of LSN and MYL2.3) Among the F_2 obtained from crosses between SHRSP/Izm and WKY/Izm. 9 rats developed stroke within 1 year after birth. One locus on Chr.4 was detected to associate with the development of stroke but not with blood pressure, indicating firstly the possible involvement of this region in the pathogenesis of stroke unrelated to hypertension itself.

将自发性高血压大鼠（SHR）或脑卒中易感大鼠（SHRSP）与正常血压 Wistar-Kyoto（WKY）大鼠杂交获得的 F_2 代，合作进行高血压和脑卒中相关基因的连锁分析。建立了 SHR/Izm、SHRSP/Izm 和 WKY/Izm 等所有参考菌株。仔细观察这些组F_2大鼠高血压、脑卒中以及与这些病理生理状况相关的其他表型的发展，并获得以下连锁分析结果。1）在3时检测到与收缩压（SBP）强连锁。染色体 (Chr.) 1 (DIMIT2)、Chr.3 (D3Mgh16) 和 Chr.4 (TRY1) 上的位点，并且在 2 处观察到不太强的连锁Chr.9和10上的位点。F_2大鼠的血压分布主要由这5个位点的遗传影响来解释。2)在Chr.1上，与SBP相关的主要基因位于距离LSN和MYL2基因位点35cM以内。 3)在从SHRSP/Izm和WKY/Izm之间杂交获得的F_2中。 9只大鼠在出生后1年内出现中风。检测到 Chr.4 上的一个位点与中风的发生有关，但与血压无关，这首先表明该区域可能参与与高血压本身无关的中风发病机制。