Recessive lethal deletion on mouse chromosome 7 affects glucocorticoid receptor binding activities

Area of Science:

• Molecular Biology
• Genetics
• Endocrinology

Background:

• Glucocorticoid receptors play a vital role in cellular regulation.
• Radiation-induced deletions on mouse chromosome 7 impact liver function, causing hypoglycemia and protein deficiencies.

Purpose of the Study:

• To investigate the effect of specific radiation-induced deletions (c14CoS) on glucocorticoid receptor binding activity in mouse liver.
• To determine if these deletions affect the structural integrity or regulatory function of glucocorticoid receptors.

Main Methods:

• Scatchard analysis of [3H]dexamethasone binding to liver extracts from control and mutant mice.
• DNA-cellulose column chromatography to assess receptor-DNA complex formation.
• Sucrose density gradient centrifugation to determine receptor sedimentation coefficients.

Main Results:

• Homozygosity for c14CoS deletions reduced glucocorticoid receptor binding activity by approximately 75% in mouse liver.
• Binding affinity (Kd) remained similar, but total binding capacity was significantly lower in mutants.
• Receptor's ability to bind DNA and sedimentation properties were unaltered, indicating no structural defect.

Conclusions:

• The deleted gene sequences are crucial for the regulation, not the structure, of glucocorticoid receptors.
• These findings have implications for understanding hormone receptor regulation and associated metabolic disorders.