| First Author | Johnson KR | Year | 2007 |
| Journal | Mol Endocrinol | Volume | 21 |
| Issue | 7 | Pages | 1593-602 |
| PubMed ID | 17440044 | Mgi Jnum | J:121821 |
| Mgi Id | MGI:3712355 | Doi | 10.1210/me.2007-0085 |
| Citation | Johnson KR, et al. (2007) Congenital hypothyroidism dwarfism and hearing impairment caused by a missense mutation in the mouse dual oxidase 2 gene, Duox2. Mol Endocrinol 21(7):1593-602 |
| abstractText | 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. |
