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

以自发性高血压大鼠（SHR）或易卒中SHR（SHRSP）与其对照的正常血压Wistar-Kyoto（WKY）大鼠（SHR/Izm、SHRSP/Izm和WKY/Izm）为参照系，进行F_2代高血压和脑卒中相关基因的连锁分析。通过对F_2代大鼠高血压、脑卒中及其他相关表型的观察，获得了以下连锁分析结果：1）在染色体（Chr.）上的3个位点与收缩压（SBP）有较强的连锁; 1（DIMIT 2）、3（D3 Mgh 16）和4（TRY 1）的基因座间存在连锁关系，而9和10号染色体上的2个基因座间存在较弱的连锁关系。2）在Chr.1上，与SBP相关的主效基因位于距离LSN和MYL 2基因座35 cM的范围内。3）在SHRSP/Izm和WKY/Izm杂交的F_2中，与SBP相关的主效基因位于距离LSN和MYL 2基因座35 cM的范围内。9只大鼠出生后1年内发生脑卒中。在Chr.4上的一个位点被检测到与中风的发展相关，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。

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.