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5'-Flanking and Intragenic Sequences Confer Androgenic and Developmental Regulation of Mouse Aldose Reductase-Like Gene in Vas Deferens and Adrenal in Transgenic Mice¹

UMR Centre National de la Recherche Scientifique 6547, Reproduction et Développement, Université Blaise Pascal Clermont II, Complexe Universitaire des Cézeaux, and Unité de Transfert de gènes dans les cellules Animals et Humaines, Complexe Universitaire des Cézeaux (S.G.), 63177 Aubiere Cedex; and INSERM U-129, Physiologie et Pathologie Génétiques et Moléculaires, Institut Cochin de Génétique Moléculaire, Université René Descartes (A.K.), 75014 Paris, France

Address all correspondence and requests for reprints to: Dr. Antoine Martinez, Reproduction et Développement, Université Blaise Pascal Clermont II, Complexe Universitaire des Cézeaux, 24 avenue des Landais, 63177 Aubiere Cedex, France. E-mail: martinez{at}cicsun.univ-bpclermont.fr

The MVDP (mouse vas deferens protein) gene, which encodes an aldose reductase-like enzyme, is mainly expressed in vas deferens epithelium and adrenal cortex. Vas deferens MVDP gene transcription was known to be under androgenic control, we now have evidence for androgen and probable ACTH responsiveness of the MVDP gene in the adrenal. To analyze the role of potential regulatory regions in hormonal, developmental, and tissue-specific aspects of MVDP regulation, we generated transgenic mice harboring MVDP-CAT fusion genes. The constructs carried either -1.8 or -0.5 kb 5'-flanking sequence attached to the chloramphenicol acetyltransferase gene in presence or absence of a 3.5-kb intragenic fragment in a downstream position.

We show that at least two regions ensure proper gene regulation in vivo. The first, located within the 1.8-kb promoter fragment, directs tissue specificity; positive elements necessary for vas deferens and adrenal expression lay within positions -1804 to -510 and -510 to +41, respectively. The second, located within the 3.5-kb intragenic fragment spanning intron 1 to intron 2, increases percentage of expressing lines and behaves as a vas deferens-specific enhancer. Hormonal and developmental control of transgenes closely parallel endogenous gene regulation. Androgen and ACTH responsiveness in adrenals is conferred by 0.5-kb promoter, whereas in vas deferens, full androgenic response of the 1.8-kb promoter required the 3.5-kb intragenic fragment. Thus, vas deferens and adrenals use distinct cis-acting elements to direct and regulate the expression of the MVDP gene.

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