Thyroid hormone receptor beta is required for thyrotrpin regulation and thyroid hormone production.

Thyroid hormone receptor beta (THRB) is post-translationally modified by small ubiquitin-like modifier (SUMO). To investigate the biological role of THRB sumoylation, we generated a mouse model with a mutation that disrupts sumoylation at lysine 146 (K146Q). The THRB K146Q mutant mice had normal serum thyroxine (T4), markedly elevated serum thyrotropin (TSH) (81-fold above control), and enlargement of both the pituitary and the thyroid gland. The marked elevation in TSH, despite a normal serum T4 concentration, indicated blunted feedback regulation of TSH. TH profuction was 10-fold lower (per mg of thyroid tissue) in mutant mice compared to Wt mice. Generated a THRB mutant mouse model that disrupted sumoylation at lysine K146 of THRB. The mutaiton is located in the 2nd zinc finger area. The funcitonal test and sturcture analysis indicated that the K146Q mutation did not alter THRB binding to a consensus DR4-TRE. Age-matched 3 months old males of wt and TRbK146Q mutant mice were used in the studyies. Thyroid hormone and pituitary thyoroid stimulating hormone (TSH) were analyzed. The hypothalamus-pituitary-thyroid axis regulation was examined by RNA-seq. Tissues from 3 mice of each genotype were desected and used in RNA-seq.