Physiological characterization of the hypertensive transgenic rat
tgr(mren2)27 harbouring the murine ren-2 gene.
Lee, Min Ae, Manfred B[diaeresis]ohm, Martin Paul, Michael Bader,
Ursula Ganten, and Detlev Ganten.
Max-Delbr[umlaut]uck-Center for Molecular Medicine (MDC), Berlin
-Buch, Germany, Institute of Clinical Pharmacology,
Universit[umlaut]atsklinikum Benjamin Franklin, Berlin, Germany
APStracts 3:0046E, 1996.
Transgenic techniques represent powerful tools for the study of gene
-related mechanisms of diseases, such as hypertension, which results
from a complex interaction between genetic and environmental factors.
The renin-angiotensin system, a biochemical cascade in which renin
functions as the key enzyme in the formation of the effector peptide
angiotensin II, plays a major role in the regulation of blood
pressure. The renin gene, therefore, represents an important
candidate gene for hypertension. Since rats are more suited than mice
for a number of experimental settings often employed in
cardiovascular research, we modified the transgenic technique to
generate the transgenic rat strain TGR(mREN2)27 harbouring the murine
Ren-2-gene. These transgenic rats develop fulminant hypertension at
an early age despite low levels of renin in plasma and kidney. In
addition, high expression of the transgene in a number of extrarenal
tissues is associated with increased local formation of angiotensin
II. Thus, the TGR(mREN2)27-rat represents a model of hypertension
with a defined genetic background. Studies on the transgenic rat may
not only provide new insights into pathophysiological mechanisms of
hypertension in this animal model, but may also offer the unique
possibility to investigate the function and regulation of renin
-angiotensin systems in extrarenal tissues. The aim of this review is
to compile the knowledge that has been accumulated on the transgenic
rat to date and to discuss possible mechanisms responsible for the
hypertensive phenotype.
Received 5 October 1996; accepted in final form 19 February 1996.
APS Manuscript Number E490-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96