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

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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 isoenzyme2–4. Experiments with hypertensive rats5,6 and some7–9, but not other10–13, 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.

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Krege, J., John, S., Langenbach, L. et al. Male–female differences in fertility and blood pressure in ACE-deficient mice. Nature 375, 146–148 (1995) doi:10.1038/375146a0

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