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.