Influence of dietary iodine deficiency on the thyroid gland in Slc26a4-null mutant mice

We evaluated the thyroid volume in histological sections with the use of three-dimensional reconstitution software, we measured serum levels of total tri-iodothyronine (TT3) and total thyroxine (TT4) levels, and we studied the thyroid gland morphology by transmission electron microscopy.TT4 levels became low but TT3 levels did not change significantly after eight weeks of an iodine-deficient diet compared to levels in the control diet animals. Even in Slc26a4-null mice fed an iodine-deficient diet, the volume of the thyroid gland did not increase although the size of each epithelial cell increased with a concomitant decrease of thyroid colloidal area.An iodine-deficient diet did not induce goiter in Slc26a4-null mice, suggesting that other environmental, epigenetic or genetic factors are involved in goiter development in PDS.Pendred syndrome (PDS) is an autosomal recessive disorder characterized by sensorineural hearing impairment, presence of goiter, and a partial defect in iodine organification [1]. The goiter in PDS is variable in its presentation; it can develop at any age (although generally after puberty), but may be totally absent in some affected individuals [2]. Also, there is substantial intrafamilial and regional variation, and nutritional iodine intake may be a significant modifier of the thyroid phenotype [1]. Kopp et al. suggested that under conditions of sufficient iodine intake, thyroid enlargement may be very mild or absent, and hence these patients are often simply categorized as having enlarged vestibular aqueduct [1]. Sato et al. also suggested that even in patients with impaired iodide transport, high iodine intake may prevent the development of goiter [3].Slc26a4-null (Slc26a4-/-) mutant mice were generated by Everett et al. [2]. Slc26a4-/- mice are profoundly deaf with vestibular dysfunction, but they lack goiter and thyroid histological abnormalities. We hypothesized that the absence of goiter and hypothyroidism in Slc26a4-/- mice was due to