HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Le, T. H. Articles by Coffman, T. M. Search for Related Content PubMed PubMed Citation Articles by Le, T. H. Articles by Coffman, T. M.

A GT-AT_1A receptor transgene protects renal cortical structure in AT₁ receptor-deficient mice

¹ Departments of Medicine and Pathology, Duke University and Durham Veterans Affairs Medical Centers, Durham 27705
² Department of Pathology, University of North Carolina, Chapel Hill, North Carolina 27599
³ Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033

To understand the physiological role of angiotensin type 1 (AT₁) receptors in the proximal tubule of the kidney, we generated a transgenic mouse line in which the major murine AT₁ receptor isoform, AT_1A, was expressed under the control of the P1 portion of the -glutamyl transpeptidase (GT) promoter. In transgenic mice, this promoter has been shown to confer cell-specific expression in epithelial cells of the renal proximal tubule. To avoid random integration of multiple copies of the transgene, we used gene targeting to produce mice with a single-copy transgene insertion at the hypoxanthine phosphoribosyl transferase (Hprt) locus on the X chromosome. The physiological effects of the GT-AT_1A transgene were examined on a wild-type background and in mice with targeted disruption of one or both of the murine AT₁ receptor genes (Agtr1a and Agtr1b). On all three backgrounds, GT-AT_1A transgenic mice were healthy and viable. On the wild-type background, the presence of the transgene did not affect development, blood pressure, or kidney structure. Despite relatively low levels of expression in the proximal tubule, the transgene blunted the increase in renin expression typically seen in AT₁-deficient mice and partially rescued the kidney phenotype associated with Agtr1a^–/–Agtr1b^–/– mice, significantly reducing cortical cyst formation by more than threefold. However, these low levels of cell-specific expression of AT₁ receptors in the renal proximal tubule did not increase the low blood pressures or abolish sodium sensitivity, which are characteristic of AT₁ receptor-deficient mice. Although our studies do not clearly identify a role for AT₁ receptors in the proximal tubules of the kidney in blood pressure homeostasis, they support a major role for these receptors in modulating renin expression and in maintaining structural integrity of the renal cortex.

proximal tubule; blood pressure; glomerular cysts

This article has been cited by other articles:

				S. Park and L. M. Harrison-Bernard Augmented Renal Vascular nNOS and Renin Protein Expression in Angiotensin Type 1 Receptor Null Mice J. Histochem. Cytochem., April 1, 2008; 56(4): 401 - 414. [Abstract] [Full Text] [PDF]