Congenital hypothyroidism, dwarfism, and hearing impairment caused by a missense mutation in the mouse dual oxidase 2 gene, Duox2

Mol Endocrinol. 2007 Jul;21(7):1593-602. doi: 10.1210/me.2007-0085. Epub 2007 Apr 17.


Dual oxidases generate the hydrogen peroxide needed by thyroid peroxidase for the incorporation of iodine into thyroglobulin, an essential step in thyroid hormone synthesis. Mutations in the human dual oxidase 2 gene, DUOX2, have been shown to underlie several cases of congenital hypothyroidism. We report here the first mouse Duox2 mutation, which provides a new genetic model for studying the specific function of DUOX2 in the thyroid gland and in other organ systems where it is hypothesized to play a role. We mapped the new spontaneous mouse mutation to chromosome 2 and identified it as a T>G base pair change in exon 16 of Duox2. The mutation changes a highly conserved valine to glycine at amino acid position 674 (V674G) and was named "thyroid dyshormonogenesis" (symbol thyd) to signify a defect in thyroid hormone synthesis. Thyroid glands of mutant mice are goitrous and contain few normal follicles, and anterior pituitaries are dysplastic. Serum T(4) in homozygotes is about one-tenth the level of controls and is accompanied by a more than 100-fold increase in TSH. The weight of adult mutant mice is approximately half that of littermate controls, and serum IGF-I is reduced. The cochleae of mutant mice exhibit abnormalities characteristic of hypothyroidism, including a delayed formation of the inner sulcus and tunnel of Corti and an abnormally thickened tectorial membrane. Hearing thresholds of adult mutant mice are on average 50-60 decibels (dB) above those of controls.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Base Sequence
  • Body Weight
  • Cochlea / pathology
  • Congenital Hypothyroidism / blood
  • Congenital Hypothyroidism / enzymology*
  • Congenital Hypothyroidism / genetics*
  • Congenital Hypothyroidism / pathology
  • DNA Primers / genetics
  • Disease Models, Animal
  • Dual Oxidases
  • Dwarfism / enzymology*
  • Dwarfism / genetics*
  • Female
  • Flavoproteins / chemistry
  • Flavoproteins / genetics*
  • Flavoproteins / physiology
  • Hearing Loss / enzymology*
  • Hearing Loss / genetics*
  • Hearing Loss / pathology
  • Hearing Loss / physiopathology
  • Homozygote
  • Humans
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Molecular Sequence Data
  • Mutation, Missense*
  • NADPH Oxidases / chemistry
  • NADPH Oxidases / genetics*
  • NADPH Oxidases / physiology
  • Phenotype
  • Pregnancy
  • Sequence Homology, Amino Acid
  • Thyrotropin / blood
  • Thyroxine / blood


  • DNA Primers
  • Flavoproteins
  • Insulin-Like Growth Factor I
  • Thyrotropin
  • Dual Oxidases
  • NADPH Oxidases
  • DUOX2 protein, human
  • Duox1 protein, mouse
  • Thyroxine