SELECTIVE RESTORATION OF MALE-FERTILITY IN MICE LACKING ANGIOTENSIN-CONVERTING ENZYMES BY SPERM-SPECIFIC EXPRESSION OF THE TESTICULAR ISOZYME

Although angiotensin-converting enzyme (ACE) has been studied primaril y in the context of its role in blood pressure regulation, this widely distributed enzyme has many other physiological functions. The ACE ge ne encodes two isozymes. The somatic isozyme is expressed in many tiss ues, including vascular endothelial cells, renal epithelial cells, and testicular Leydig cells, whereas the testicular or germinal angiotens in-converting enzyme is expressed only in sperm. The ACE gene knockout mice lack both isozymes and they exhibit low blood pressure, kidney d ysfunctions, and male infertility. Here, we report the use of a sperm- specific promoter and interbreeding of transgenic and gene knockout mi ce for generating a mouse strain that expressed ACE only in sperm. The experimental mice maintained the kidney defects of ACE-/- mice, but u nlike the knockout strain, the males were fertile. Thus, we establishe d that the role of ACE in male fertility is completely dependent on it s exclusive expression in sperm. Our study clearly demonstrated how tr ansgenic and knockout techniques can be combined for ascribing a speci fic physiological function to the expression of a multifunctional prot ein in a given tissue.