title: Molecular genetic analysis of glucocorticoid signalling in development.
abstract: A null mutation of the glucocorticoid receptor was generated by homologous recombination. Mutant newborn mice showed impaired lung development, hypertrophy of the adrenal cortex and a strongly reduced size of the adrenal medulla. Phenylethanolamine N-methyltransferase (PNMT) was undetectable in the adrenals of the mutant mice. Serum levels of corticosterone were moderately and ACTH levels were strongly elevated in the mutants. A weaker but significant increase of corticosterone and ACTH was observed already in heterozygous animals. This points to a dysregulation of the HPA axis due to defective feedback regulation via the glucocorticoid receptor. Liver gluconeogenetic enzymes were reduced to a variable degree. Whereas survival of heterozygous mutants was not affected, most of the homozygous mutant mice died during the perinatal period.
authors.affiliation: Division Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg.
authors.forename: W
authors.initials: W
authors.lastname: Schmid
authors.forename: T J
authors.initials: TJ
authors.lastname: Cole
authors.forename: J A
authors.initials: JA
authors.lastname: Blendy
authors.forename: G
authors.initials: G
authors.lastname: Schütz
mesh_terms: D000818:Animals; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011965:Receptors, Glucocorticoid / Q000502:physiology*
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid