The glucocorticoid hormone signal transduction pathway in mice homozygous for chromosomal deletions causing failure of cell type-specific inducible gene expression.
Wild-type newborn mice are characterized by the ability of certain liver-specific genes encoding various enzymes and mapping on different chromosomes to respond to glucocorticoid induction. Newborn mice homozygous for deletions at and around the albino locus on chromosome 7 fail to develop this competence for hormone-inducible gene expression even through they do show normal constitutive expression of the same genes. Studies of the glucocorticoid hormone signal transduction pathway reported here show identical expression of glucocorticoid receptor mRNA and protein in deletion homozygotes and normal littermates. Furthermore, the receptor interacts normally with the 90-kDa heat shock protein hsp90. Elevated glucocorticoid hormone levels in newborn deletion homozygotes, most likely resulting from their stressed condition, provide an explanation for the reduced binding activities of receptors reported previously. The elimination of receptors and hormones as direct targets of the chromosomal deletion effects suggests that the failure of inducible gene expression might reside in defective competence of the affected structural genes to respond to the hormonal stimulus.
DeFranco
D
D
Department of Biological Sciences, University of Pittsburgh, PA 15260.
Bali
D
D
Torres
R
R
DePinho
R A
RA
Erickson
R P
RP
Gluecksohn-Waelsch
S
S
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002872:Chromosome Deletion; D003907:Dexamethasone / Q000378:metabolism; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000378:metabolism; D006720:Homozygote; D006854:Hydrocortisone / Q000097:blood; D008099:Liver / Q000502:physiology; D046911:Macromolecular Substances; D051379:Mice; D008817:Mice, Mutant Strains; D011233:Precipitin Tests; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D015398:Signal Transduction
D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D006854:Hydrocortisone