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Adrenocortical-specific transgene expression directed by steroid hydroxylase gene promoters.

TitleAdrenocortical-specific transgene expression directed by steroid hydroxylase gene promoters.
Publication TypeJournal Article
Year of Publication1996
AuthorsMorley SD, Viard I, Parker KL, Mullins JJ
JournalEndocr Res
Volume22
Issue4
Pagination631-9
Date Published1996 Nov
ISSN0743-5800
KeywordsAdrenal Cortex, Aldosterone Synthase, Animals, beta-Galactosidase, Escherichia coli, Gene Expression, Mice, Mice, Transgenic, Promoter Regions, Genetic, Steroid 11-beta-Hydroxylase, Steroid 21-Hydroxylase, Steroid Hydroxylases, Transfection, Transgenes
Abstract

The 5'-flanking regions of genes for three mouse adrenal steroid hydroxylases were analyzed for their ability to direct adrenal cortex-specific beta-galactosidase (beta-gal) reporter expression both in cell culture and transgenic mice. The 5'-flanking regions chosen were from the genes for steroid 21-hydroxylase (21-OHase), expressed throughout the adrenal cortex and mediating both glucocorticoid and mineralocorticoid synthesis, and aldosterone synthetase (AS) and steroid 11 beta-hydroxylase (11 beta-OHase), which catalyze respectively the terminal steps of mineralocorticoid synthesis in the zona glomerulosa and glucocorticoid synthesis in the zona fasciculata/reticularis. While 5.0 kb of 11 beta-OHase gene 5'-flanking region and 5.4 kb of the AS gene 5'-flanking region mediated respectively moderate and low levels of beta-gal reporter expression in Y1 adrenocortical tumor cells, neither of these 5'-flanking regions was able to direct reporter expression to the appropriate adrenocortical zone of transgenic mice. This suggests that additional regulatory elements, lying outside these 5'-flanking regions, are required for 11 beta-OHase and AS gene expression in the intact mouse. In contrast, 6.4 kb of the mouse 21-OHase A gene 5' flanking region was able to direct specific beta-galactosidase reporter expression, in both Y1 cells and transgenic mice, indicating that elements directing adrenal cortex-specific gene expression in vivo are located not more than 6.4 kb 5' of the 21-OHase gene transcription start site.

Alternate JournalEndocr. Res.
PubMed ID8969922
Grant ListHL48460 / HL / NHLBI NIH HHS / United States