Genetic Linkages for Thyroxine Released in Response to Thyrotropin Stimulation in Three Sets of Recombinant Inbred Mice Provide Evidence for Shared and Novel Genes Controlling Thyroid Function

Background: Graves' hyperthyroidism is induced by immunizing mice with adenovirus expressing the human thyrotropin (TSH)-receptor. Using families of recombinant-inbred mice, we previously discovered that genetic susceptibility to induced thyroid-stimulating antibodies and hyperthyroidism are linked to loci on different chromosomes, indicating a fundamental genetic difference in thyroid sensitivity to ligand stimulation. An approach to assess thyroid sensitivity involves challenging genetically diverse lines of mice with TSH and measuring the genotype/strain-specific increase in serum thyroxine (T4). Methods: We investigated genetic susceptibility and genetic control of T4 stimulation by 10 mU bovine TSH in female mice of the CXB, BXH, and AXB/BXA strain families, all previously studied for induced Graves' hyperthyroidism. Results: Before TSH injection, T4 levels must be suppressed by inhibiting endogenous TSH secretion. Three daily intraperitoneal L-triiodothyronine injections efficiently suppressed serum...