Critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice

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Publication Type Journal Article
School or College College of Science; School of Medicine
Department Oncological Sciences; Biology; Human Genetics
Program Institute of Human Genetics; Howard Hughes Medical Institute (HHMI)
Creator Capecchi, Mario R.
Other Author Esther, C.R.; Marino, E.M.; Howard, T.E.; Machaud, A.; Corvol, P.; Bernstein, K.E.
Title Critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice
Date 1997-03-06
Description Angiotensin-converting enzyme (ACE) generates the vasoconstrictor angiotensin II, which plays a critical role in maintenance of blood pressure in mammals. Although significant ACE activity is found in plasma, the majority of the enzyme is bound to tissues such as the vascular endothelium. We used targeted homologous recombination to create mice expressing a form of ACE that lacks the COOH-terminal half of the molecule. This modified ACE protein is catalytically active but entirely secreted from cells. Mice that express only this modified ACE have significant plasma ACE activity but no tissue-bound enzyme. These animals have low blood pressure, renal vascular thickening, and a urine concentrating defect. The phenotype is very similar to that of completely ACE-deficient mice previously reported, except that the renal pathology is less severe. These studies strongly support the concept that the tissue-bound ACE is essential to the control of blood pressure and the structure and function of the kidney.
Type Text
Publisher American Society for Clinical Investigation,
Volume 99
Issue 10
First Page 2375
Last Page 2385
Subject Blood pressure; ACE activity; Enzyme
Subject MESH Alleles; Blood Pressure; DNA Primers; Exons; Genotype; Homozygote; Kidney; Mice, Inbred Strains; Mice, Mutant Strains; Organ Specificity; Peptidyl-Dipeptidase A; Polymerase Chain Reaction; Promoter Regions (Genetics); RNA Splicing; RNA, Messenger; Restriction Mapping; Sequence Deletion; Sex Characteristics; Superovulation; Testis; Transcription, Genetic
Language eng
Bibliographic Citation Esther, C.R., Marino, E.M., Howard, T.E., Machaud, A., Corvol, P., Capecchi, M.R., & Bernstein, K.E. (1997). The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice. The Journal of Clinical Investigation, 99(10), 2375-85. Retrieved May 2, 2006, from
Rights Management Copyright 1997 American Society for Clinical Investigation. Reproduction of material presented in the journal is governed by the fair use limitations of US copyright law (detailed at You need to request permission to reproduce material if the use is commercial or if you wish to make multiple copies other than for educational purposes (
Format Medium application/pdf
Format Extent 527,360 bytes
Identifier ir-main,95
ARK ark:/87278/s63b6hk0
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2021-05-06
ID 705782
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