Neither the New Zealand genetically hypertensive strain nor Dahl salt-sensitive strain has an A1079T transversion in the alpha 1 isoform of the Na+,K+-ATPase gene

A putative 1079A -->T mutation in the al isoform of the Na+, K+-ATPase (Atp lal) gene of the Dahl salt-sensitive rat inbred by John Rapp (SS/Jr) strain was projected to cause a conformation change in the membrane hydrophobic r egion of the protein product, possibly resulting in hypertension. The exist ence of the mutation was challenged, but the challenge was apparently rebut ted. The New Zealand genetically hypertensive (GH) rat is known to have a b lood pressure quantitative trait locus on chromosome 2 containing the gene for the ATPase. Thus, we sought to determine whether the GH rat carried the 1079A -->T transversion. We chose a method, first nucleotide change analys is, that can detect point mutations in a mixed population of polymerase cha in reaction (PCR) products, even in the presence of PCR bias, and confirmed our analysis by restriction enzyme digestion of PCR products. To ensure th e validity of our analyses, we used site-directed mutagenesis to create pos itive controls containing the mutation. Surprisingly, we found that neither the GH nor the SS/Jr strain had the A1079T transversion. Indeed, the trans version was not found in any strain tested. As an incidental observation, w e have sequenced the intron preceding the exon containing the putative A107 9T transversion. Within this intron, a single-base C/T polymorphism was obs erved at base 132. Our results definitively eliminate the putative A1079T t ransversion in Atplal as a causative factor underlying hypertension in the GH, spontaneously hypertensive, and SS/Jr rat strains and indicate that alt ernative candidate genes in the region defined by the chromosome 2 hyperten sion quantitative trait locus should be examined.