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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
Date Published1996 Nov
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

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