Specific receptors control steroid sensitivity in lymphoma cell hybrids

Insights

Glucocorticoid receptor gene mapping was advanced using mouse lymphoma cell hybrids. Wild-type sensitivity dominated resistance, and resistant cells often lost a chromosome, indicating hemizygosity of the glucocorticoid receptor gene.

Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Endocrinology

Background:

  • Mouse lymphoma cell lines, including S49.1 variants (wild-type, receptor binding-defective, nuclear transfer-defective) and EL4 (nuclear transfer-defective), were utilized.
  • Understanding glucocorticoid receptor (GR) function and gene localization is crucial in endocrinology and cancer research.

Purpose of the Study:

  • To investigate the genetic basis of glucocorticoid resistance in mouse lymphoma cells.
  • To develop a cell system for mapping the glucocorticoid receptor gene to a specific mouse chromosome.

Main Methods:

  • Hybridization of different S49.1 sub-lines with EL4 lymphoma cells.
  • Phenotypic analysis of hybrid cells for glucocorticoid sensitivity, receptor binding, and nuclear transfer.
  • Selection of resistant segregants from sensitive hybrid clones and chromosomal analysis.

Main Results:

  • Wild-type glucocorticoid sensitivity was dominant over nuclear transfer-defective resistance.
  • The receptor binding-defective and nuclear transfer-defective phenotypes did not complement, suggesting a defect in the same polypeptide.
  • Resistant segregants frequently lost a chromosome, correlating with the loss of wild-type S49.1 receptor, indicating hemizygosity of the GR gene.

Conclusions:

  • The study provides direct evidence for the hemizygosity of the glucocorticoid receptor gene in S49.1 cells.
  • The developed cell system is suitable for assigning the glucocorticoid receptor gene to a specific mouse chromosome.

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