Absence of primary hypothyroidism and goiter in Slc26a4 (-/-) mice fed on a low iodine diet.

[pendred syndrome]

Mutations in the SLC 26 A 4 gene , coding for the anion transporter pendrin , are responsible for Pendred syndrome , characterized by congenital sensorineural deafness and dyshormonogenic goiter . The physiological role of pendrin in the thyroid is still unclear and the lack of a thyroid phenotype in some patients with SLC 26 A 4 mutations and in Slc 26 a 4 (-/-) mice indicate the existence of environmental or individual modifiers able to compensate for pendrin inactivation in the thyroid . Since pendrin can transport iodide in vitro , variations in iodide supply have been claimed to account for the thyroid phenotype associated with pendrin defects .The Slc 26 a 4 (-/-) mouse model was used to test the hypothesis that iodide supply may influence the penetrance and expressivity of SLC 26 A 4 mutations .Slc 26 a 4 (-/-) and (+/+) mice were fed up to 6 months on a standard or low iodine diet and were evaluated for thyroid structural abnormalities or biochemical hypothyroidism .A 27 -fold iodide restriction induced similar modifications in thyroid histology , but no differences in thyroid size , T 4 or TSH levels were observed between between Slc 26 a 4 (-/-) and (+/+) mice , either in standard conditions and during iodine restriction .Iodide restriction is not able to induce a thyroid phenotype in Slc 26 a 4 (-/-) mice . These experimental data , together with those coming from a review of familial Pendred cases leaving in regions either with low or sufficient iodide supply , support the idea that the expression of thyroid phenotype in Pendred syndrome is more powerfully influenced by individual factors than by dietary iodide .