Hypothyroidism in transgenic mice expressing IFN-gamma in the thyroid

IFN-gamma has been implicated with contradictory results in the pathogeneti c process of autoimmune (Hashimoto's) thyroiditis, the most common cause of hypothyroidism in adults. To test whether the local production of IFN-gamm a can lead to thyroid dysfunction. we have generated transgenic mice that e xpress constitutively IFN-gamma in the thyroid follicular cells. This expre ssion resulted in severe hypothyroidism. with growth retardation and disrup tion of the thyroid architecture. The hypothyroidism derived from a profoun d inhibition of the expression of the sodium iodide symporter gene. Taken t ogether, these results indicate a direct role of IFN-gamma in the thyroid d ysfunction that occurs in autoimmune thyroiditis.