Document Detail


Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility.
MedLine Citation:
PMID:  8642790     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mammals produce two isozymes of angiotensin-converting enzyme (ACE). Somatic ACE plays an important role in the control of blood pressure. The function of testis ACE, produced by male and germ cells, is not known. To examine the roles of these isozymes, we used targeted homologous recombination to introduce a modified ACE allele into a mouse line. Mice homozygous for this mutant allele lack both ACE isozymes and have markedly reduced blood pressures. Contrary to a previous report, we found heterozygous male mice to have normal blood pressures. Homozygous mutant mice also have severe renal disease. The renal papilla is markedly reduced, and the intrarenal arteries exhibit vascular hyperplasia associated with a perivascular inflammatory infiltrate. These animals cannot effectively concentrate urine. They also have an abnormally low urinary sodium to potassium ratio despite reduced levels of aldosterone. Homozygous mutant male mice sire significantly smaller litters than wild-type male mice; however, no defect in sperm number, morphology, or motility was detected. ACE-deficient animals demonstrate the role of this enzyme in systemic blood pressure, renal development and function, and male fertility.
Authors:
C R Esther; T E Howard; E M Marino; J M Goddard; M R Capecchi; K E Bernstein
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Laboratory investigation; a journal of technical methods and pathology     Volume:  74     ISSN:  0023-6837     ISO Abbreviation:  Lab. Invest.     Publication Date:  1996 May 
Date Detail:
Created Date:  1996-07-16     Completed Date:  1996-07-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376617     Medline TA:  Lab Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  953-65     Citation Subset:  IM    
Affiliation:
Department of Pathology, Emory University, Atlanta, Georgia 30322, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
Blood Pressure*
Female
Homozygote
Infertility, Male / etiology*,  pathology,  physiopathology
Isoenzymes / blood,  deficiency,  genetics,  physiology
Kidney / enzymology,  pathology,  physiopathology
Kidney Concentrating Ability
Kidney Diseases / etiology*,  pathology,  physiopathology
Male
Mice
Mice, Mutant Strains
Molecular Sequence Data
Peptidyl-Dipeptidase A / blood,  deficiency,  genetics,  physiology*
Polymerase Chain Reaction
Recombination, Genetic
Testis / enzymology,  pathology
Water Deprivation / physiology
Grant Support
ID/Acronym/Agency:
DK39777/DK/NIDDK NIH HHS; DK44280/DK/NIDDK NIH HHS; DK45215/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Isoenzymes; EC 3.4.15.1/Peptidyl-Dipeptidase A

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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