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

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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