Published Online
on April 21, 2003

A more recent version of this article appeared on June 1, 2003

This Article Full Text (PDF) All Versions of this Article: 41/6/1212    most recent 01.HYP.0000069010.28143.5Cv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walsh, V. Articles by Samani, N. J. Search for Related Content PubMed PubMed Citation Articles by Walsh, V. Articles by Samani, N. J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Protein UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB LOSARTAN POTASSIUM SODIUM CHLORIDE Related Collections Animal models of human disease Genetically altered mice Hypertension - basic studies Genetics of cardiovascular disease

Submitted on January 29, 2002
Revised on February 24, 2003

Analysis of the Role of the SA Gene in Blood Pressure Regulation by Gene Targeting

Vanessa Walsh; Laurence Somody; Aldo Farrell; Beili Zhang; Jane Brown; Catrin Pritchard; Madeleine Vincent; and Nilesh J. Samani^*

From the Division of Cardiology, Department of Medicine, University of Leicester (V.W., A.F., N.J.S.), UK; Laboratoire de Physiologie EA 645, Faculté de Médecine Grange Blanche, Université de Lyon (L.S., B.Z., M.V.), France; the Departments of Biomedical Services (J.B.) and Biochemistry (C.P.), University of Leicester, UK.

^* To whom correspondence should be addressed. E-mail: njs{at}le.ac.uk.

Abstract--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.

Key words: hypertension, genetic • kidney • genes • genetics • renin-angiotensin system

This article has been cited by other articles:

				J.-R. Clemitson, R. J. Dixon, S. Haines, A. J. Bingham, B. R. Patel, L. Hall, M. Lo, J. Sassard, F. J. Charchar, and N. J. Samani Genetic Dissection of a Blood Pressure Quantitative Trait Locus on Rat Chromosome 1 and Gene Expression Analysis Identifies SPON1 As a Novel Candidate Hypertension Gene Circ. Res., April 13, 2007; 100(7): 992 - 999. [Abstract] [Full Text] [PDF]

				C. A. Hinojos, E. Boerwinkle, M. Fornage, and P. A. Doris Combined Genealogical, Mapping, and Expression Approaches to Identify Spontaneously Hypertensive Rat Hypertension Candidate Genes Hypertension, April 1, 2005; 45(4): 698 - 704. [Abstract] [Full Text] [PDF]

				M. R. Garrett, H. Meng, J. P. Rapp, and B. Joe Locating a Blood Pressure Quantitative Trait Locus Within 117 kb on the Rat Genome: Substitution Mapping and Renal Expression Analysis Hypertension, March 1, 2005; 45(3): 451 - 459. [Abstract] [Full Text] [PDF]

				C. Areste, M J. Melia, J. Isern, J. L. Tovar, and A. Meseguer Sex steroid regulation and identification of different transcription units of the SA gene in mouse kidney J. Endocrinol., October 1, 2004; 183(1): 101 - 114. [Abstract] [Full Text] [PDF]

				S. E. Whitesall, J. B. Hoff, A. P. Vollmer, and L. G. D'Alecy Comparison of simultaneous measurement of mouse systolic arterial blood pressure by radiotelemetry and tail-cuff methods Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2408 - H2415. [Abstract] [Full Text] [PDF]