Date Thesis Awarded


Access Type

Honors Thesis -- Open Access

Degree Name

Bachelors of Science (BS)




Dr. Lizabeth Allison

Committee Members

Dr. Randolph Coleman

Dr. Diane Shakes

Dr. Patty Zwollo


Thyroid hormone plays a vital role in growth and metabolism. Its action is mediated by multiple receptors including thyroid hormone receptor α 1 (TRα1). TRα1 is primarily a nuclear protein, but it has been found to shuttle rapidly between the nucleus and cytoplasm. Recently, mutated variants of TRα1 have been found to cause Resistance to Thyroid Hormone α syndrome (RTHα). Over 20 different mutations in patients have been described including amino acid substitutions at position 384 in human (h) TRα1 from arginine (R) to either cysteine (C) or histidine (H). One of the potential mechanisms of the disorder is mislocalization of the receptor within the cell. To test this hypothesis, the distribution of these two TRα1 mutations associated with RTHα was assessed by fluorescence microscopy after transfection of HeLa (human) cells with expression plasmids for GFP-tagged hTRα1_R384C and hTRα1_R384H. Both RTHα mutants were found to have a significantly larger cytoplasmic population than wild type TRα1. This suggests that the mislocalization of the receptor within the cell could contribute to the symptoms of RTHα.