Fuchs, Sebastien; Xiao, Hong D.; Cole, Justin M.; Adams, Jonathan W.; Frenzel, Kristen; MIchaud, Annie; Zhao, Hui; Keshelava, George; Corvol, Pierre; Bernstein, Kenneth E.
citation_title
Role of the N-terminal catalytic domain of angiotensin-converting enzyme investigated by targeted inactivation in mice
citation_date
2004-02-13
Description
Angiotensin-converting enzyme (ACE) produces the vasoconstrictor angiotensin II. The ACE protein is composed of two homologous domains, each binding zinc and each independently catalytic. To assess the physiologic significance of the two ACE catalytic domains, we used gene targeting in mice to introduce two point mutations (H395K and H399K) that selectively inactivated the ACE N-terminal catalytic site. This modification does not affect C-terminal enzymatic activity or ACE protein expression. In addition, the testis ACE isozyme is not affected by the mutations. Analysis of homozygous mutant mice (termed ACE 7/7) showed normal plasma levels of angiotensin II but an elevation of plasma and urine N-acetyl-Ser-Asp-Lys-Pro, a peptide suggested to inhibit bone marrow maturation. Despite this, ACE 7/7 mice had blood pressure, renal function, and hematocrit that were indistinguishable from wild-type mice.
Type
text;
citation_publisher
American Society for Biochemistry and Molecular Biology (ASBMB)
citation_journal_title
Journal of Biological Chemistry
citation_volume
279
citation_issue
16
citation_firstpage
15946
Citation_lastpage
15953
citation_doi
10.1074/jbc.M400149200
citatation_issn
0021-9258
citation_language
eng;
Bibliographic Citation
Fuchs, S., Xiao, H. D., Cole, J. M., Adams, J. W., Frenzel, K., Michaud, A., Keshelava, G., Capecchi, M. R., Corvol, P., & Bernstein, K. E. (2004). Role of the N-terminal catalytic domain of angiotensin-converting enzyme investigated by targeted inactivation in mice. Journal of Biological Chemistry, 279, 15946-53.
