Journal article
Functional expression of the human angiotensinogen gene in transgenic mice
The Journal of biological chemistry, Vol.269(51), pp.32497-32502
12/23/1994
DOI: 10.1016/s0021-9258(18)31662-4
PMID: 7798251
Abstract
The renin-angiotensin system is a major determinant of arterial pressure and volume homeostasis in mammals through the actions of angiotensin II, the proteolytic digestion product of angiotensinogen. Molecular genetic studies in several human populations have revealed genetic linkage between the angiotensinogen gene and both hypertension and increased plasma angiotensinogen. Transgenic mice were generated with a human angiotensinogen genomic clone to develop an animal model to examine tissue- and cell-specific expression of the gene and to determine if overexpression of angiotensinogen results in hypertension. Human angiotensinogen mRNA was expressed in transgenic mouse liver, kidney, heart, adrenal gland, ovary, brain, and white and brown adipose tissue and, in kidney, was exclusively localized to epithelial cells of the proximal convoluted tubules. Plasma levels of human angiotensinogen were approximately 150-fold higher in transgenic mice than that found normally in human plasma. The blood pressure of mice bearing the human angiotensinogen gene was normal but infusion of a single bolus dose of purified human renin resulted in a transient increase in blood pressure of approximately 30 mm Hg within 2 min. These results suggest that abnormalities in the angiotensinogen gene resulting in increased circulating levels of angiotensinogen could potentially contribute in part to the pathogenesis of essential hypertension.
Details
- Title: Subtitle
- Functional expression of the human angiotensinogen gene in transgenic mice
- Creators
- Gongyu Yang - University of IowaDavid C Merrill - University of Iowa Hospitals and ClinicsMark W ThompsonJean E Robillard - University of IowaCurt D Sigmund - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.269(51), pp.32497-32502
- DOI
- 10.1016/s0021-9258(18)31662-4
- PMID
- 7798251
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Grant note
- HL48058 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/23/1994
- Academic Unit
- Molecular Physiology and Biophysics; Nephrology, Dialysis and Transplantation; Stead Family Department of Pediatrics; Neuroscience and Pharmacology; Medicine Administration
- Record Identifier
- 9984774211802771
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