Molecular Genetic Analysis of Glucocorticoid Signaling Using the Cre/loxP System
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Holger M. Reichardt
Abstract
Glucocorticoids (GC) are involved in a plethora of physiological processes that range from the regulation of the stress response and the control of the immune system to modulation of behavior. Most GC effects are mediated by the glucocorticoid receptor (GR) via activation and repression of gene expression. Whereas in most cases activation requires DNA binding of the receptor, repression is usually mediated by protein-protein interaction with other transcription factors. To decipher the molecular mode of action of GR, mice were generated by gene targeting carrying a point mutation in one of the dimerization domains, thus abrogating DNA binding by GR. Analysis of these mice demonstrated that thymocyte apoptosis and stress erythropoiesis require the DNA binding-dependent function of GR, whereas lung development and the anti-inflammatory activity of GR are mediated by protein-protein interaction. Furthermore, to study the role of GC in the brain, mice were generated specifically lacking GR function in the nervous system. Using these mice we demonstrated that GR is essential for the regulation of the HPA-axis and the stress response, as well as for the control of emotional behavior. Taken together, gene targeting using the Cre/loxP system proved to be highly valuable for the analysis of both molecular mechanism and tissue-specific functions of the GR.
Copyright © 2000 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Alexander J. Varshavsky Felix Hoppe-Seyler Lecturer 2000
- The Ubiquitin System and the N-End Rule Pathway
- Paper of the Year 1999: Award to Igor Stagljar
- A Clockwork Organ
- The Transgeneticists Toolbox: Novel Methods for the Targeted Modification of Eukaryotic Genomes
- Interdependence of Filamentous Actin and Microtubules for Asymmetric Cell Division
- Genetic Analysis of Mammalian Cyclin-Dependent Kinases and Their Inhibitors
- Phosphorylcholine Substituents in Nematodes: Structures, Occurrence and Biological Implications
- Selenium in Biology: Facts and Medical Perspectives
- The Role of Se, Mo and Fe in the Structure and Function of Carbon Monoxide Dehydrogenase
- Molecular Basis for Interactions of the DnaK Chaperone with Substrates
- Protein Import: the Hitchhikers Guide into Chloroplasts
- Pathway Analysis and Metabolic Engineering in Corynebacterium glutamicum
- Metabolic Networks: a Signal-Oriented Approach to Cellular Models
- Representing and Analysing Molecular and Cellular Function Using the Computer
- Protein Aggregation and Pathogenesis of Huntingtons Disease: Mechanisms and Correlations
- The Mitochondrial Protein Import Motor
- The Immunoglobulin κ Gene Families of Human and Mouse: a Cottage Industry Approach
- Protein-Protein Interactions in Receptor Activation and Intracellular Signalling
- Molecular Genetic Analysis of Glucocorticoid Signaling Using the Cre/loxP System
- Macromolecular Intelligence in Microorganisms
- Thyroid Hormone Receptors Bind to an Element in the Connexin43 Promoter
- Analysis of the Deubiquitinating Enzymes of the Yeast Saccharomyces cerevisiae
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- Surface Topography of Microtubule Walls Decorated with Monomeric and Dimeric Kinesin Constructs
- Histone Deacetylase Activity Is Required for the Induction of the MyoD Muscle Cell Lineage in Xenopus
- The Effect of Heat Shock on 20S/26S Proteasomes
- Sec61p Is the Main Ribosome Receptor in the Endoplasmic Reticulum of Saccharomyces cerevisiae
