Expression of the 11β-hydroxysteroid dehydrogenase 2 gene in the mouse. Aldosterone acts via mineralocorticoid receptors (MRs) to control salt and water flux in epithelial organs such as the kidney and colon to maintain circulatory homeostasis. Inappropriate glucocorticoid-mediated activation of MRs in aldosterone-target tissues is prevented by the glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD2). We have studied HSD2 expression in the mouse at the level of gene transcription and further analyzed, with HSD1, its pattern of tissue-restricted gene expression. The mouse HSD2 gene, including upstream regulatory regions, has been cloned, and its transcription start site has been mapped in colon and kidney. A 2.5 kb upstream region has been sequenced, and its proximal promoter region has been analyzed. We have compared the relative expression of HSD1 and HSD2 in a variety of tissues from male mice using ribonuclease protection analysis. HSD1 was expressed in liver, kidney, adrenal, lung, spleen, thymus, fat, small intestine, stomach, heart, skin, and epididymis. HSD2 was expressed in kidney, colon, small intestine, stomach, and epididymus. No expression of either HSD1 and HSD2 was detected in bladder, testis, seminal vesicles, vas deferens, prostate, or skeletal muscle. Finally, to investigate the specific roles of HSD2 in vivo, we have created “floxed” HSD2 alleles using gene targeting in mouse embryonic stem cells with the aim to create tissue-specific ablation of HSD2 in mice via Cre recombinase mediated gene targeting.