7 RENIN ALLELES IN RATS AND THEIR EFFECTS ON BLOOD-PRESSURE

Objective: To survey inbred rat strains for renin alleles and to test those alleles for effects on blood pressure. Design: Rat strains with renin alleles different from the s allele carried by inbred Dahl salt- sensitive (SS/Jr) rats were crossed with SS/Jr rats and subsequently i ntercrossed to produce F-2 populations. Thus, in each F-2 population s egregation of the s renin allele and a contrasting renin allele occurr ed. F-2 rats were raised on a high-salt diet and their blood pressures were determined. The cosegregation of renin alleles with blood pressu re was evaluated in each F-2 population. Methods: Renin alleles were r ecognized by the variable number of tandem repeats in the first intron of the ren in gene and by a variable HindIII site in the fifth intron . Genotyping was by restriction fragment length polymorphism analysis. Results: Seven renin alleles were found, but breeding stock for only six of these alleles was available. From these stocks it was possible to construct five F-2 populations in which the s renin allele segregat ed with a contrasting renin allele. In all five F-2 populations the ra ts homozygous for the s allele had higher blood pressure than those ho mozygous for the contrasting renin allele, but statistical significanc e was most easily established in the F-2 intercrossed offspring of an SS/Jr x inbred Dahl salt-resistant (SR/Jr) rat cross. This result was duplicated. Conclusions: There are at least seven alleles in rats at t he renin locus, allowing many pairwise allelic comparisons to be made. Of the five alleles compared with the s renin allele, the r allele of SR/Jr rats was unique in providing strong evidence for cosegregation with blood pressure. The naive expectation that all crosses should yie ld the same cosegregation result with blood pressure for a candidate l ocus is not consistent with either theory or the present experimental results.