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(Received for publication, April 23, 1997, and in revised form, August 6, 1997)
From the Transgenic mice were generated
containing a 1542-base pair fragment of the kidney androgen-regulated
protein (KAP) promoter fused to the human angiotensinogen
(HAGT) gene with the goal of specifically targeting
inducible expression of renin-angiotensin system components to the
kidney. High level expression of both KAP-HAGT and
endogenous KAP mRNA was evident in the kidney of male mice from two
independent transgenic lines. Renal expression of the transgene in
female mice was undetectable under basal conditions but could be
strongly induced by administration of testosterone. Testosterone
treatment did not cause a transcriptional induction in any other
tissues examined. However, an analysis of six androgen target tissues
in males revealed that the transgene was expressed in epididymis. No
other extra-renal expression of the transgene was detected. In
situ hybridization demonstrated that expression of
HAGT (and KAP) mRNA in males and testosterone-treated
females was restricted to proximal tubule epithelial cells in the renal cortex. Although there was no detectable human angiotensinogen protein
in plasma, it was evident in the urine, consistent with a pathway of
synthesis in proximal tubule cells and release into the tubular lumen.
These results demonstrate that 1542 base pairs of the KAP promoter is
sufficient to drive expression of a heterologous reporter gene in a
tissue-specific, cell-specific, and androgen-regulated fashion in
transgenic mice.
Volume 272, Number 44,
Issue of October 31, 1997
pp. 28142-28148
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
The Kidney Androgen-regulated Protein Promoter Confers Renal
Proximal Tubule Cell-specific and Highly Androgen-responsive
Expression on the Human Angiotensinogen Gene in Transgenic
Mice
,
,
,
and§
Genetics Program, § Departments
of Internal Medicine and Physiology & Biophysics, ** Department of
Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa
City, Iowa 52242 and 
The Population Council, The Rockefeller
University, New York, New York 10021
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