Volume 2, Number 1, March 2001

Lessons on renal function from transgenic mice lacking different angiotensin II receptors
William J Arendshorst

Over the past decade, investigators have refined and capitalised on powerful gene targeting technology in animals to investigate the cellular and integrative physiology and pathophysiology of such complex diseases as atherosclerosis and essential hypertension.^1-3 Precise genetic interventions, utilising homologous recombination in mouse embryonic stem cells, have provided novel insights into the importance of the renin-angiotensin-aldosterone system (RAAS) in the control of kidney function as well as other tissues and organs. Significant loss of function during renal development and in the regulation of haemodynamics, epithelial transport, excretion of salt and water, and arterial blood pressure (BP) have been elucidated. The genetic absence of specific actions of different angiotensin II (Ang II) AT-receptors results in characteristic phenotypes, some of which have marked abnormalities, whereas others are barely detectable. The resultant multilayered collages reflect graded functional absence or presence of a selected protein, combined with physiological homeostatic adjustments by remaining effective components of the renin-angiotensin system. Compensatory responses of these and other systems contribute significantly to the final phenotypic characteristics. Careful investigation of these genetically-engineered model systems should contribute to our understanding of how naturally occurring mutations of genes in the renin-angiotensin family cause or contribute to disease processes such as hypertension. This brief review will survey studies that have used gene targeting to evaluate AT-receptor function on the kidney to gain insight into regulatory mechanisms in renal vascular and tubular cells. For additional information, the reader is referred to many recent excellent reviews on this subject.^4-9

JRAAS 2001;2:167-175.

View full PDF article (open in new window)
Export to bibliographic software or plain text
Email this article