Expression of Renin in Large Arteries Outside the Kidney Revealed by Human Renin Promoter/LacZ Transgenic Mouse

• Published in: The American journal of pathology Vol. 161; no. 2; pp. 717 - 725
• Main Authors: Fuchs, Sébastien, Germain, Stéphane, Philippe, Josette, Corvol, Pierre, Pinet, Florence
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01-08-2002; ASIP; American Society for Investigative Pathology; American Society for Investigative Pathology / Elsevier
• Subjects: Animal Models; Animals; Arterial hypertension. Arterial hypotension; Arteries - metabolism; beta-Galactosidase; Biological and medical sciences; Blood and lymphatic vessels; Cardiology and cardiovascular system; Cardiology. Vascular system; Experimental diseases; Human health and pathology; Humans; Kidney - metabolism; Lac Operon; Life Sciences; Medical sciences; Mice; Mice, Transgenic; Promoter Regions, Genetic; Renin - biosynthesis; Renin - genetics; Hypertension; Immunohistochemistry; Animal model; Enzyme; Rodentia; Transgenic animal; Cardiovascular disease; Artery; Promoter; Pathology; Peptidases; Vertebrata; Mammalia; Renin; Mouse; Animal; Hydrolases; Arterial pressure; Aspartic endopeptidases; Molecular biology
• ISSN: 0002-9440; 1525-2191
• DOI: 10.1016/S0002-9440(10)64227-7

Renin plays a central role in controlling blood pressure as it catalyzes the first step in the production of angiotensin II. The aim of this study was to isolate fragments of the human renin (hREN) promoter able to direct tissue-specific and regulated expression of a LacZ reporter gene mimicking endogenous renin. We screened several hREN promoter/LacZ constructs for transgene expression in transient embryos at
E15
when renin expression begins. We found that a 12-kb hREN promoter conferred high expression in the kidney at both embryonic and adult stages and that the transgene was expressed in the same cells as endogenous renin. We explored two pathophysiological models in which renin is stimulated and showed concomitant increases in β-galactosidase and renin activities.
In situ
β-galactosidase staining showed renin/transgene-expressing cells are recruited in the juxtaglomerular apparatus and in the afferent arterioles as well as in larger arteries outside the kidney. Using our model, renin expression in interlobular arteries was confirmed as being striped and, for the first time, expression of renin in larger arteries outside the kidney was shown. Therefore, this strain is a suitable model to investigate renin gene pathophysiological regulations
in vivo
.