Holger M. Reichardt, François Tronche, Anton Bauer, Günther Schütz
Molecular Genetic Analysis of Glucocorticoid Signaling Using the Cre/loxP System
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.
Biological Chemistry, Walter de Gruyter
Print ISSN: 1431-6730
Volume: 381, 09/2000
Pages: 961 - 964
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