Restriction fragment length polymorphisms mapped in spontaneously hypertensive rats using kallikrein probes

We have explored the role of kallikrein-kinin system in essential hypertension using spontaneously hypertensive rats (SHR) as an animal model. A rat tissue kallikrein complementary (c) DNA (RSK 1105) was used as a probe in Southern blot hybridization to detect restriction fragment length polymorphisms (RFLPs) in SHR. Using 23 different restriction endonucleases, we have identified five RFLPs involving alterations in restriction fragment lengths for the restriction enzymes Bgl II, Dra I, Nde I, Sph I, and Bcl I. Three of the enzymes, Nde I, Sph I, and Bgl II, generate multiple polymorphic fragments. We have further mapped these RFLPs with two additional probes, both from the rat renal kallikrein gene RSKG 7. The 5' probe, consisting of sequences approximately 2000 base pair (bp) 5' of the first exon, recognizes RFLPs in DNA digested with Bcl I and Sph I. The 3' probe, approximately 4400 bp away from the fifth exon, recognizes polymorphic fragments in DNA digested with Bcl I, Dra I and Nde I. These findings indicate possible differences in tissue kallikrein genes or their regulatory regions in SHR that could contribute to the pathogenesis of hypertension in this animal model.