Induction of goitrous hypothyroidism by dietary iodide in SJL mice.

Prolonged intake of large amounts of iodide has been reported to increase the incidence of goiter and/or hypothyroidism in humans as well as animals prone to spontaneous autoimmune thyroiditis. In the current study, we investigated the role of dietary iodide on the development of hypothyroidism, as well as thyroiditis, in strains of mice that do not develop spontaneous autoimmune thyroiditis. Intake of 0.05% NaI via drinking water for 10 wk induced hypothyroidism in SJL/J mice as indicated by elevated TSH and depressed total T(4) values in serum and formation of colloidal goiter with an inactive flattened thyroid epithelium. Hypothyroidism did not appear to have an autoimmune basis because only focal mononuclear cell infiltrates were found intrathyroidally, and antithyroglobulin antibodies or increased organification of iodide were not detected. These phenomena were not observed in similarly treated CBA/J mice, suggesting polymorphisms in genes controlling events downstream of iodide uptake by thyrocytes. Interestingly, RT-PCR analysis indicated that unlike CBA/J, SJL/J mice could not down-regulate Na/I symporter gene expression during the NaI treatment. No significant temporal or strain differences were observed regarding the expression of thyroglobulin, pendrin, thyroid peroxidase, and DUOX1 and DUOX2 genes after NaI intake. Our results point to the generation of a mouse model for the study of iodine-induced hypothyroidism, which does not seem to have an autoimmune basis.