Evaluation of steroid receptor function by gene targeting in mice

J Steroid Biochem Mol Biol. 2005 Feb;93(2-5):107-12. doi: 10.1016/j.jsbmb.2004.12.033. Epub 2005 Feb 3.


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.

MeSH terms

  • Alleles
  • Animals
  • Brain / metabolism
  • Chromosomes, Artificial, Bacterial / genetics
  • Cognition / physiology
  • Feedback
  • Gene Targeting / methods*
  • Hypothalamo-Hypophyseal System / physiology
  • Immune System / metabolism
  • Liver / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Mineralocorticoid Receptor Antagonists
  • Mutagenesis
  • Pituitary-Adrenal System / physiology
  • Receptors, Glucocorticoid / antagonists & inhibitors
  • Receptors, Glucocorticoid / deficiency
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / physiology
  • Receptors, Mineralocorticoid / deficiency
  • Receptors, Mineralocorticoid / genetics
  • Receptors, Mineralocorticoid / physiology
  • Receptors, Steroid / antagonists & inhibitors
  • Receptors, Steroid / deficiency
  • Receptors, Steroid / genetics*
  • Receptors, Steroid / physiology*


  • Mineralocorticoid Receptor Antagonists
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • Receptors, Steroid