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(Circulation Research. 2005;96:1135.)
© 2005 American Heart Association, Inc.

Review

Six Truisms Concerning ACE and the Renin-Angiotensin System Educed From the Genetic Analysis of Mice

Kenneth E. Bernstein, Hong D. Xiao, Kristen Frenzel, Ping Li, Xiao Z. Shen, Jon W. Adams, Sebastien Fuchs

From the Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Ga.

Correspondence to Dr Ken Bernstein, Rm 7107A WMB, Department of Pathology, 101 Woodruff Cir, Atlanta, GA 30322. E-mail kbernst@emory.edu

This Review is part of a thematic series on Angiotensin Converting Enzyme, which includes the following articles:

Six Truisms Concerning ACE and the Renin-Angiotensin System Educed From the Genetic Analysis of Mice

ACE and Vascular Remodeling ACE II in the Heart and the Kidney

ACE Signaling

ACE Polymorphisms
Rudi Bussi Editors

Key Words: angiotensin • renin-angiotensin system • mouse • cardiovascular disease • angiotensin converting enzyme

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
The history of the renin-angiotensin system (RAS) is one of marvelous discoveries extending from Robert Tigerstedt’s naming renin in 1898 to the present time; biochemists, physiologists, pharmacologists, and practicing clinicians have all combined to describe the physiologic implications of converting angiotensinogen into angiotensin II. Indeed, one may argue that the clinical development of ACE inhibitors and angiotensin II receptor antagonists has benefited humankind to a level seen only with the development of antibiotics and steroids. As we begin the twenty-first century, it is worthwhile to summarize the state of our knowledge concerning ACE and angiotensin II. In doing, we benefit from a whole class of experiments not available to those writing reviews even 10 years ago: the revolution in our ability to genetically manipulate the mouse as an experimental model. This is due to the widespread application of gene targeting by homologous recombination in embryonic stem cells. As is widely appreciated, this technology can produce a knockout mouse lacking any particular gene. Less appreciated are the full capabilities of this methodology which can be summarized as: if it can be dreamed, it can be done. Gene targeting can be used to create point mutations, duplicate a gene, and modify the expression pattern of a protein almost as easily as creating knockout mice null for a particular protein. We, and others, have used gene targeting in mice to create modifications in the renin-angiotensin system of a sort not seen in humans. While any single experiment may be assailed as not representing . . . [Full Text of this Article]

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