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A gammaGT-AT1A receptor transgene protects renal cortical structure in AT1 receptor-deficient mice.

Publication ,  Journal Article
Le, TH; Oliverio, MI; Kim, H-S; Salzler, H; Dash, RC; Howell, DN; Smithies, O; Bronson, S; Coffman, TM
Published in: Physiol Genomics
August 11, 2004

To understand the physiological role of angiotensin type 1 (AT(1)) receptors in the proximal tubule of the kidney, we generated a transgenic mouse line in which the major murine AT(1) receptor isoform, AT(1A), was expressed under the control of the P1 portion of the gamma-glutamyl transpeptidase (gammaGT) 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 gammaGT-AT(1A) transgene were examined on a wild-type background and in mice with targeted disruption of one or both of the murine AT(1) receptor genes (Agtr1a and Agtr1b). On all three backgrounds, gammaGT-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 AT(1)-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 AT(1) receptors in the renal proximal tubule did not increase the low blood pressures or abolish sodium sensitivity, which are characteristic of AT(1) receptor-deficient mice. Although our studies do not clearly identify a role for AT(1) 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.

Duke Scholars

Published In

Physiol Genomics

DOI

EISSN

1531-2267

Publication Date

August 11, 2004

Volume

18

Issue

3

Start / End Page

290 / 298

Location

United States

Related Subject Headings

  • gamma-Glutamyltransferase
  • X Chromosome
  • Transgenes
  • Survival
  • Renin
  • Recombinant Fusion Proteins
  • Receptor, Angiotensin, Type 1
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Organ Specificity
 

Citation

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MLA
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Le, T. H., Oliverio, M. I., Kim, H.-S., Salzler, H., Dash, R. C., Howell, D. N., … Coffman, T. M. (2004). A gammaGT-AT1A receptor transgene protects renal cortical structure in AT1 receptor-deficient mice. Physiol Genomics, 18(3), 290–298. https://doi.org/10.1152/physiolgenomics.00120.2003
Le, Thu H., Michael I. Oliverio, Hyung-Suk Kim, Harmony Salzler, Rajesh C. Dash, David N. Howell, Oliver Smithies, Sarah Bronson, and Thomas M. Coffman. “A gammaGT-AT1A receptor transgene protects renal cortical structure in AT1 receptor-deficient mice.Physiol Genomics 18, no. 3 (August 11, 2004): 290–98. https://doi.org/10.1152/physiolgenomics.00120.2003.
Le TH, Oliverio MI, Kim H-S, Salzler H, Dash RC, Howell DN, et al. A gammaGT-AT1A receptor transgene protects renal cortical structure in AT1 receptor-deficient mice. Physiol Genomics. 2004 Aug 11;18(3):290–8.
Le, Thu H., et al. “A gammaGT-AT1A receptor transgene protects renal cortical structure in AT1 receptor-deficient mice.Physiol Genomics, vol. 18, no. 3, Aug. 2004, pp. 290–98. Pubmed, doi:10.1152/physiolgenomics.00120.2003.
Le TH, Oliverio MI, Kim H-S, Salzler H, Dash RC, Howell DN, Smithies O, Bronson S, Coffman TM. A gammaGT-AT1A receptor transgene protects renal cortical structure in AT1 receptor-deficient mice. Physiol Genomics. 2004 Aug 11;18(3):290–298.

Published In

Physiol Genomics

DOI

EISSN

1531-2267

Publication Date

August 11, 2004

Volume

18

Issue

3

Start / End Page

290 / 298

Location

United States

Related Subject Headings

  • gamma-Glutamyltransferase
  • X Chromosome
  • Transgenes
  • Survival
  • Renin
  • Recombinant Fusion Proteins
  • Receptor, Angiotensin, Type 1
  • RNA, Messenger
  • Promoter Regions, Genetic
  • Organ Specificity