Juxtaglomerular cell expression and partial regulation of a human
renin genomic transgene driven by a minimal renin promoter.
Sinn, Patrick L., Xiaoji Zhang, and Curt D. Sigmund.
Departments of Internal Medicine and Physiology & Biophysics, The
University of Iowa College of Medicine, Iowa City, Iowa 52242
APStracts 6:0104F, 1999.
In the kidney, renin gene expression is exquisitely localized to the
juxtaglomerular cells lining the afferent arteriole having the
capacity to regulate renin synthesis in response to a variety of
physiological cues. We investigated human renin gene expression in
transgenic mice containing a genomic construct driven by 149bp of its
proximal promoter to elucidate whether this was sufficient to confer
juxtaglomerular-specific expression. While human renin mRNA was
permissively expressed in most tissues, the transgene was expressed
mainly in juxtaglomerular cells in the kidney. Active human renin and
human prorenin was found in the systemic circulation at levels
consistent with previous transgenic models. Remarkably, two lines
displayed an appropriate up-regulation of transgene mRNA in response
to ACE inhibition, and two lines exhibited a down-regulation of
transgene mRNA in response to subpressor and pressor doses of Ang-II.
Our results suggest that 149bp of the human renin proximal promoter,
in a context of a genomic construct, is sufficient to confer human
renin expression in renal JG cells and at least some aspects of
appropriate regulation.
Received 16 March 1999; accepted in final form 21 May 1999.
APS Manuscript Number F070-9.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 14 June 1999