A new genetic locus cosegregating with blood pressure in F2 progeny obtained from stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats.

BACKGROUND

Segregation studies using genomic polymorphisms on F2 progeny obtained from hypertensive rat models showed that a putative hypertensive gene is located close to the angiotensin converting enzyme (ACE) gene. However, it was suggested that additional major genes should contribute to the pathogenesis of hypertension.

METHODS

F2 rats were obtained from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats of Izumo colony. Blood pressure was measured with a photoelectronic oscillometric tail-cuff method before and during salt loading. Genomic DNA was extracted from livers and digested with HaeIII or Rsal. DNA fingerprinting was performed with 26 32P-labelled human variable number of tandem repeats markers.

RESULTS

Eighty-seven fingerprint bands polymorphic between SHRSP and WKY were obtained. When the distribution of these bands in the F2 progeny was studied, one fingerprint band (1/MCT96.1) showed a distorted distribution between the high- and low-blood pressure subpopulations of the F2 rats, suggesting that the band cosegregated with blood pressure. When blood pressure was compared between the F2 rats with [(+) rats] and without [(-) rats] the 1/MCT96.1 band, it was found that (-) rats had significantly higher basal and salt-loaded blood pressures than (+) rats. The 1/MCT96.1 locus was also shown to have no positive linkage with the ACE locus.

CONCLUSION

The present study showed that examination of the allele distribution between subpopulations with extreme phenotype can be used in the screening of loci cosegregating with blood pressure. Furthermore, a locus not in the ACE region, showing cosegregation with blood pressure in F2 progeny from SHRSP and WKY rats, was found.