Adrenocortical-specific transgene expression directed by steroid hydroxylase gene promoters

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Abstract
The 5′-flanking regions of genes for three mouse adrenal steroid hydroxylases were analyzed for their ability to direct adrenal cortex-specific β-galactosidase (β-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 11β-hydroxylase (11β-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 11β-OHase gene 5′-flanking region and 5.4 kb of the AS gene 5′-flanking region mediated respectively moderate and low levels of β-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 11β-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 β-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.