MALE-FEMALE DIFFERENCES IN FERTILITY AND BLOOD-PRESSURE IN ACE-DEFICIENT MICE

ANGIOTENSIN-CONVERTING enzyme (ACE) is a dipeptidyl carboxypeptidase t hat generates the vasoconstricting peptide angiotensin II and inactiva tes the vasodilating peptide bradykinin(1). The gene encoding ACE is c omposed of two homologous regions and codes for both a somatic and tes tis 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 f orm 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 sperma togenic cells and sperm(15). Its function is unknown(16) Here we inves tigate the role of the Ace gene in blood pressure control and reproduc tion using mice generated to carry an insertional mutation that is des igned to inactivate both forms of ACE. All homozygous female mutants w ere found to be fertile, but the fertility of homozygous male mutants was greatly reduced. Heterozygous males but not females had blood pres sures that were 15-20 mm Hg less than normal, although both male and f emale heterozygotes had reduced serum ACE activity.