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

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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.