Journal article
Highly Regulated Cell Type-restricted Expression of Human Renin in Mice Containing 140- or 160-Kilobase Pair P1 Phage Artificial Chromosome Transgenes
The Journal of biological chemistry, Vol.274(50), pp.35785-35793
12/1999
DOI: 10.1074/jbc.274.50.35785
PMID: 10585461
Abstract
We generated transgenic mice with two P1 artificial chromosomes, each containing the human renin (HREN) gene and extending to -35 and -75 kilobase pairs, respectively. HREN protein production was restricted to juxtaglomerular cells of the kidney, and its expression was tightly regulated by angiotensin II and sodium. The magnitude of the up- and down-regulation in HREN mRNA caused by the stimuli tested was identical to the endogenous renin gene, suggesting tight physiological regulation. P1 artificial chromosome mice were mated with transgenic mice overexpressing human angiotensinogen to determine if there was a chronic compensatory down-regulation of the transgene. Despite a 3-fold down-regulation of HREN mRNA, plasma angiotensin II and blood pressure was modestly elevated in the double transgenic mice. Nevertheless, this elevation was significantly less than a different double transgenic model containing a poorly regulated HREN transgene. The increase in blood pressure, despite the decrease in HREN mRNA, suggests that the HREN gene can partially, but not completely, compensate for excess circulating angiotensinogen. These data suggest the possibility that increases in circulating or tissue angiotensinogen may cause an increase in blood pressure in humans, even in the presence of a functionally active servo-mechanism to down-regulate HREN expression.
Details
- Title: Subtitle
- Highly Regulated Cell Type-restricted Expression of Human Renin in Mice Containing 140- or 160-Kilobase Pair P1 Phage Artificial Chromosome Transgenes
- Creators
- Patrick L SinnDeborah R DavisCurt D Sigmund
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.274(50), pp.35785-35793
- DOI
- 10.1074/jbc.274.50.35785
- PMID
- 10585461
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 12/1999
- Academic Unit
- Molecular Physiology and Biophysics; Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Pathology; Neuroscience and Pharmacology
- Record Identifier
- 9984093492002771
Metrics
18 Record Views