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Published on: September 28, 2015
Angiotensin-converting enzyme 2 gene targeting studies in mice: mixed messages
Susan B Gurley1, Thomas M Coffman
1Division of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, Durham, NC, USA.
Abstract:
As a major regulator of blood pressure homeostasis, the renin-angiotensin system (RAS) has been the subject of extensive scientific investigation. While the RAS was first discovered more than 100 years ago, several novel components of the system have been identified only in the last decade. One of these newer members of the RAS family is angiotensin-converting enzyme 2 (ACE2). Among the approaches used to establish a physiological role for ACE2 has been the generation of ACE2-null mouse lines using homologous recombination in embryonic stem cells. In the literature, there have been at least three lines of ACE2 knockout mice generated by gene targeting by different investigative groups. Interestingly, there are significant differences in some of the reported phenotypes of these distinct lines, especially with regard to their cardiovascular physiology. In this paper, we will review the results of published experiments using these ACE2-null mouse lines, highlighting similarities and differences in these studies and summarizing their contributions to our understanding of the physiological functions of this novel member of the RAS.
Insights
Investigating angiotensin-converting enzyme 2 (ACE2) knockout mice reveals varied cardiovascular phenotypes. This review compares distinct ACE2-null mouse lines to clarify ACE2
Area of Science:
- Physiology
- Cardiovascular Science
- Endocrinology
Background:
- The renin-angiotensin system (RAS) is crucial for blood pressure regulation.
- Angiotensin-converting enzyme 2 (ACE2) is a recently identified component of the RAS.
- Understanding ACE2's physiological role is essential.
Purpose of the Study:
- To review and compare published studies utilizing ACE2-null mouse lines.
- To highlight discrepancies in reported cardiovascular phenotypes among different ACE2 knockout models.
- To synthesize findings regarding the physiological functions of ACE2.
Main Methods:
- Generation of ACE2-null mouse lines via homologous recombination in embryonic stem cells.
- Analysis of phenotypes, particularly cardiovascular physiology, across distinct ACE2 knockout models.
- Literature review of experimental results from different investigative groups.
Main Results:
- Multiple ACE2 knockout mouse lines have been generated by different research groups.
- Significant variations exist in the reported cardiovascular phenotypes of these distinct lines.
- Comparison of these lines aids in understanding ACE2's complex physiological roles.
Conclusions:
- ACE2-null mouse models provide valuable insights into the physiological functions of ACE2.
- Discrepancies in phenotypes underscore the need for careful interpretation of knockout mouse data.
- Further research is needed to fully elucidate the role of ACE2 in cardiovascular homeostasis.

