Analysis of the role of the SA gene in blood pressure regulation by gene targeting.

The SA gene is expressed in the proximal tubule of the kidney and may be involved in blood pressure (BP) regulation. However, direct evidence for this is lacking. We constructed and analyzed an SA-null mouse in which exons 2 and 3 of the SA gene (including the start codon) had been deleted by homologous recombination. Basal BP and BP changes in response to increased salt and to treatment with losartan were compared between mice homozygous for the targeted SA allele (SA-/- mice) and littermates carrying the wild-type allele (SA+/+ mice). Molecular and biochemical analysis confirmed the lack of SA gene product in SA-/- mice. SA-/- mice grew normally, were fertile, and had no overt phenotype. With both indirect and direct techniques, basal BP was similar in SA-/- and SA+/+ mice. A high salt diet for 4 weeks caused a significant increase in BP in SA-/- and SA+/+, mice but there was no difference between the 2 strains. Losartan caused a significant decrease in BP, but again the response was similar between SA-/- and SA+/+ mice, as were their kidney renin mRNA levels. SA is not involved in the regulation of either basal or salt related BP, and the lack of differential effect in SA-/- mice is not a consequence of compensatory activation of the renin-angiotensin system.