Seven 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 intercrossed to produce F2 populations. Thus, in each F2 population segregation of the s renin allele and a contrasting renin allele occurred. F2 rats were raised on a high-salt diet and their blood pressures were determined. The cosegregation of renin alleles with blood pressure was evaluated in each F2 population. METHODS: Renin alleles were recognized by the variable number of tandem repeats in the first intron of the renin 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 F2 populations in which the s renin allele segregated with a contrasting renin allele. In all five F2 populations the rats homozygous for the s allele had higher blood pressure than those homozygous for the contrasting renin allele, but statistical significance was most easily established in the F2 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 the 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 yield the same cosegregation result with blood pressure for a candidate locus is not consistent with either theory or the present experimental results.