Resistance to Thyroid Hormone (RTH) syndrome is a developmental disease characterized by the failure of peripheral tissues to respond to thyroid hormone signaling. A382PfsX7 is a nonfunctional RTH-associated variant of thyroid hormone receptor α1 which fails to bind thyroid hormone and disassociate from corepressors. The mutation also deletes a nuclear export signal (NES) from the C-terminal end of the receptor. This thesis sought to determine whether this NES deletion altered the intracellular distribution of TR in a way which would imply interference with its role in transcriptional activation and repression. Using lipid-based transfection of fluorescently-labeled TR into HeLa (human) cells and fluorescent microscopy, the nuclear-to-cytoplasmic ratio of wild-type (WT) and mutant TR and the presence of TR aggregates was evaluated. Coexpression of WT-TRα1 and A382PfsX7 is associated with a cytosolic shift in localization and an increased frequency of TR aggregation. These data suggest that novel interactions between WT and mutant receptors may increase the aggregation propensity of TR and thereby alter localization
