B6(129)-Duox2^thyd/J

Stock number: 005543
Product name: thyroid dyshormonogenesis
Research areas: Endocrine Deficiency Research, Internal/Organ Research, Mouse/Human Gene Homologs, Neurobiology Research, Reproductive Biology Research, Sensorineural Research

Description

These mice carry a recessive spontaneous mutation of the Duox2 gene that results in a defect in thyroid hormone synthesis.

Detailed description

The mouse Duox2^thyd mutation provides a 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. The Duox2^thyd mutation is mapped to chromosome 2 and identified 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" 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.

Development

The thyroid dyshormonogenesis mutation arose spontaneously in the B6.129-Tnfrsf1a^tm1Mak/J strain (stock #002818) at The Jackson Laboratory in 2000. After one backcross to C57BL/6J the offspring were intercrossed and the N1F2 progeny were genotyped for the Tnfrsf1a^tm1Mak mutation. Those lacking this targeted mutation were selected as breeders to continue the line, which has been maintained by breeding heterozygous males with hosts of homozygous ovarian transplantation. In 2007 this strain reached generation N1F6.

Allele

Symbol: Duox2^thyd
Name: thyroid dyshormonogenesis
MGI accession ID: MGI:3712359
Generation method: Spontaneous
Marker symbol: Duox2
Marker name: dual oxidase 2
Chromosome: 2
Strain of origin: B6.129-Tnfrsf1a^tm1Mak/J
Molecular note: A spontaneous T-to-G transition (A-to-C on forward strand) in exon 16 causes a change from a highly conserved valine to glycine at amino acid position 674 (p.V674G).