Male–female differences in fertility and blood pressure in ACE-deficient mice

Abstract

ANGIOTENSIN-CONVERTING enzyme (ACE) is a dipeptidyl carboxy-peptidase that generates the vasoconstricting peptide angiotensin II and inactivates the vasodilating peptide bradykinin¹. The gene encoding ACE is composed of two homologous regions and codes for both a somatic and testis isoenzyme^2–4. Experiments with hypertensive rats^5,6 and some^7–9, but not other^10–13, studies of humans suggest that sequences at or linked to the gene influence blood pressure. The testis-specific form of ACE has its own promoter within intron 12 (ref. 14), is encoded by the 3′ region of the gene, and is found only in postmeiotic spermatogenic cells and sperm¹⁵. Its function is unknown¹⁶. Here we investigate the role of the Ace gene in blood pressure control and reproduction using mice generated to carry an insertional mutation that is designed to inactivate both forms of ACE. All homozygous female mutants were found to be fertile, but the fertility of homozygous male mutants was greatly reduced. Heterozygous males but not females had blood pressures that were 15–20 mm Hg less than normal, although both male and female heterozygotes had reduced serum ACE activity.