Gene targeting in physiological investigations: studies of the
renin angiotensin system.
Coffman, Thomas M.
Division of Nephrology, Department of Medicine, Duke University and
Durham VA Medical Centers
APStracts 5:0044F, 1998.
Gene targeting using homologous recombination in embryonic stem (ES)
cells provides an avenue for the direct application of precise
molecular genetic interventions to the study of complex systems in
whole animals. As such, it represents a powerful approach for
physiological investigation. Although its applications in physiology
were initially limited because of technical difficulties in
performing whole animal experiments in mice, these difficulties have
been rapidly overcome and gene targeting has been used productively
in physiological experimentation. Studies that have been performed
using mice in which genes in the renin-angiotensin system (RAS) have
been altered by gene targeting, illustrate both the feasibility and
the utility of this technique for addressing physiological issues.
These studies have demonstrated novel roles for the RAS in the
development and maintenance of kidney structure and they have added
to the understanding of how RAS gene products regulate blood pressure
and renal function. Finally, these experiments may contribute to
understanding how naturally-occurring mutations in RAS genes cause
hypertension.
Received 3 October 1997; accepted in final form 12 February 1998.
APS Manuscript Number F320-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 19 February 1998