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Pregnancy-Induced Changes in Renin Gene Expression in Mice¹

^a Departments of Biochemistry and Molecular Biology and ^b Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, Texas 77030 ^c Cardiovascular Center, Cornell University Medical College, New York, New York 10021 ^d Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

A puzzling feature of the renin-angiotensin system during pregnancy is the appearance in the maternal circulation of a large increase in the concentration of prorenin and renin. The physiologic role of these changes is not understood. We determined that high levels of renin protein occur in the circulation of pregnant mice, thereby establishing the mouse as a valuable model for understanding gestation-induced changes in the renin-angiotensin system. We used the murine model to show that high levels of renin gene expression occur at the mother-fetus interface, first in maternal decidua and subsequently in placentas. These results were obtained using ICR mice that have 2 related renin genes, Ren1 and Ren2. We also examined renin gene expression in C57Bl/6 mice that have only the Ren1 gene. In these mice, very little renin gene expression was observed in placentas but instead was upregulated in kidneys during pregnancy. In both ICR and C57Bl/6 mice, there is an increase in renin protein in the maternal circulation during pregnancy. However, these mice differ with regard to gestation-induced sites of increased renin gene expression. These studies suggest that mice are a convenient and valuable model for studying renin gene expression during pregnancy.

First decision: 6 July 2001.

¹ This work was supported by a grant from the National Institutes of Health (HD34130) to R.E.K. and by a National Institutes of Health training grant (T32-HD07324) to Y.X.

² Correspondence: Rodney E. Kellems, Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, 6431 Fannin, Houston, TX 77030. FAX: 713 500 0652; rodney.e.kellems{at}uth.tmc.edu

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