Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility.
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.
Esther
C R
CR
Department of Pathology, Emory University, Atlanta, Georgia 30322, USA.
Howard
T E
TE
Marino
E M
EM
Goddard
J M
JM
Capecchi
M R
MR
Bernstein
K E
KE
D000818:Animals; D001483:Base Sequence; D001794:Blood Pressure; D005260:Female; D006720:Homozygote; D007248:Infertility, Male / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007527:Isoenzymes / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D007668:Kidney / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D007671:Kidney Concentrating Ability; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D013737:Testis / Q000201:enzymology / Q000473:pathology; D014868:Water Deprivation / Q000502:physiology
D007527:Isoenzymes; D007703:Peptidyl-Dipeptidase A