title: Absence of primary hypothyroidism and goiter in Slc26a4 (-/-) mice fed on a low iodine diet.
abstract: BACKGROUND
  Mutations in the SLC26A4 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 SLC26A4 mutations and in Slc26a4 (-/-) 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.
  
  
  OBJECTIVE
  The Slc26a4 (-/-) mouse model was used to test the hypothesis that iodide supply may influence the penetrance and expressivity of SLC26A4 mutations.
  
  
  METHODS
  Slc26a4 (-/-) 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.
  
  
  RESULTS
  A 27-fold iodide restriction induced similar modifications in thyroid histology, but no differences in thyroid size, T4 or TSH levels were observed between between Slc26a4 (-/-) and (+/+) mice, either in standard conditions and during iodine restriction.
  
  
  CONCLUSIONS
  Iodide restriction is not able to induce a thyroid phenotype in Slc26a4 (-/-) 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.
authors.affiliation: Department of Medical Sciences, University of Milan, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Calebiro
authors.forename: P
authors.initials: P
authors.lastname: Porazzi
authors.forename: M
authors.initials: M
authors.lastname: Bonomi
authors.forename: S
authors.initials: S
authors.lastname: Lisi
authors.forename: A
authors.initials: A
authors.lastname: Grindati
authors.forename: D
authors.initials: D
authors.lastname: De Nittis
authors.forename: L
authors.initials: L
authors.lastname: Fugazzola
authors.forename: M
authors.initials: M
authors.lastname: Marinò
authors.forename: G
authors.initials: G
authors.lastname: Bottà
authors.forename: L
authors.initials: L
authors.lastname: Persani
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics* / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D006042:Goiter / Q000503:physiopathology*; D006044:Goiter, Nodular / Q000235:genetics / Q000503:physiopathology; D006319:Hearing Loss, Sensorineural / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007037:Hypothyroidism / Q000503:physiopathology*; D007455:Iodine / Q000008:administration & dosage* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D000076988:Sulfate Transporters; D013961:Thyroid Gland / Q000166:cytology / Q000473:pathology / Q000502:physiology; D013972:Thyrotropin / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism
chemical_list: D027321:Anion Transport Proteins; C494849:Slc26a4 protein, mouse; D000076988:Sulfate Transporters; D013972:Thyrotropin; D007455:Iodine; D013974:Thyroxine