Recessive lethal deletion on mouse chromosome 7 affects glucocorticoid receptor binding activities.
The hormone binding activity of glucocorticoid receptors is decreased by approximately equal to 75% in the livers of mice homozygous for c14CoS, one of several overlapping radiation-induced deletions on chromosome 7. These deletions have been shown previously to map at and around the albino (c) locus and to act as recessive lethals. They are associated with intractable hypoglycemia, ultrastructural abnormalities in certain liver cell membranes, and deficiencies of specific liver proteins and enzymes that are induced by insulin or glucocorticoids, or both. Scatchard analysis of [3H]dexamethasone binding to receptors in control and mutant liver extracts revealed that the glucocorticoid binding constants were similar; however, the control extracts bound approximately equal to 4 times as much steroid as did mutant extracts. Analysis by DNA-cellulose column chromatography demonstrated that the ability of activated glucocorticoid receptors to form complexes with DNA appears to be unaltered in the mutants; both mutant and control cytosols contain glucocorticoid receptors that elute from DNA-cellulose columns at two different salt concentrations. Sucrose density gradient centrifugation revealed the glucocorticoid receptors in mutant livers to have approximately the same sedimentation coefficient as receptors in control livers. The decrease in glucocorticoid binding activity in mutant liver cell extracts is comparable in degree to that previously reported for insulin binding activity. The gene sequences deleted in the homozygous deletion mutants appear to be instrumental in the regulation rather than the structural determination of both glucocorticoid and insulin receptors.
D000818:Animals; D002499:Centrifugation, Density Gradient; D002872:Chromosome Deletion; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D011987:Receptors, Steroid; D003907:Dexamethasone; D004247:DNA