Loss of glucocorticoid receptor function in the pituitary results in early postnatal lethality.
Glucocorticoid action in the brain is mediated by the glucocorticoid receptor (GR) and the mineralocorticoid receptor, thereby affecting physiological processes such as neurogenesis, synaptic plasticity, and neuroendocrine control. To examine GR function in the regulation of the hypothalamic-pituitary-adrenal axis, we generated GR mutant mice that are homozygous for a conditional GR allele and heterozygous for a transgene that expresses the Cre recombinase under control of the regulatory elements of the mouse calcium/calmodulin-dependent protein kinase IIalpha gene, resulting in Cre-mediated recombination in the brain and pituitary. The GR mutants die about 1 wk after birth and display a fulminant increase in plasma corticosterone as well as a severe histopathological phenotype. To assess in which time frame targeting of the pituitary occurs during embryonic development, we used a transgenic line expressing an inducible CreER(T2) fusion protein under the control of the regulatory elements of the calcium/calmodulin-dependent protein kinase IIalpha gene. Cre reporter data show that pituitary targeting occurred during embryonic development at the time when glucocorticoid synthesis starts.
Erdmann
Gitta
G
German Cancer Research Center, Division Molecular Biology of the Cell I, Im Neuenheimer Feld 280, Heidelberg, Germany.
Schütz
Günther
G
Berger
Stefan
S
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D005938:Glucocorticoids / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D019426:Integrases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010902:Pituitary Gland / Q000378:metabolism*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000324:Adrenocorticotropic Hormone; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C045073:Cre recombinase; D019426:Integrases; D003345:Corticosterone