| First Author | Wintermantel TM | Year | 2005 |
| Journal | J Steroid Biochem Mol Biol | Volume | 93 |
| Issue | 2-5 | Pages | 107-12 |
| PubMed ID | 15860252 | Mgi Jnum | J:242125 |
| Mgi Id | MGI:5904467 | Doi | 10.1016/j.jsbmb.2004.12.033 |
| Citation | Wintermantel TM, et al. (2005) Evaluation of steroid receptor function by gene targeting in mice. J Steroid Biochem Mol Biol 93(2-5):107-12 |
| abstractText | Corticosteroid hormones regulate a variety of developmental, physiological and pathological processes via their cognate receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). Using modern genetic technologies, including bacterial artificial chromosome-based transgenesis and conditional gene targeting, we have generated a panel of tissue-specific and function-selective mutations of the two corticosteroid hormone receptors in the mouse. These mouse models have allowed us to gain new insights into corticosteroid hormone signaling in vivo. By investigating a hepatocyte-specific GR mutation, it has been possible to define a novel biological action of GR, namely to function as a coactivator for Stat5-mediated gene transcription in the control of body growth. The investigation of brain-specific mutations have not only allowed us to better understand hypothalamo-pituitary-adrenal (HPA) axis regulation by glucocorticoids, but also to analyse corticosteroid action in various aspects of brain function like anxiety-related or addiction-related behaviour, and learning and memory. A function-selective mutation in the GR has allowed us to dissect different pathways in the gene expression regulation by this receptor, namely to separate DNA response element-binding dependent gene activation from response element-independent gene regulation via interference with other transcription factors. These different transcriptional activities of GR play an important role in glucocorticoid-mediated immunosuppression. |
