Publication Type |
Journal Article |
School or College |
College of Science |
Department |
Biology |
Creator |
Capecchi, Mario R. |
Other Author |
Fuchs, Sebastien; Xiao, Hong D.; Cole, Justin M.; Adams, Jonathan W.; Frenzel, Kristen; MIchaud, Annie; Zhao, Hui; Keshelava, George; Corvol, Pierre; Bernstein, Kenneth E. |
Title |
Role of the N-terminal catalytic domain of angiotensin-converting enzyme investigated by targeted inactivation in mice |
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 |
Publisher |
American Society for Biochemistry and Molecular Biology (ASBMB) |
Journal Title |
Journal of Biological Chemistry |
Volume |
279 |
Issue |
16 |
First Page |
15946 |
Last Page |
15953 |
DOI |
10.1074/jbc.M400149200 |
citatation_issn |
0021-9258 |
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. |
Rights Management |
(c)American Society for Biochemistry and Molecular Biology (ASBMB) http://dx.doi.org/10.1074/jbc.M400149200 |
Format Medium |
application/pdf |
Format Extent |
394,182 bytes |
Identifier |
ir-main,9127 |
ARK |
ark:/87278/s6bk1wn4 |
Setname |
ir_uspace |
ID |
704110 |
Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6bk1wn4 |