B6(Cg)-Tpo^tee-2J/GrsrJ

Stock number: 026224
Research areas: Developmental Biology Research, Endocrine Deficiency Research, Internal/Organ Research, Metabolism Research, Reproductive Biology Research, Sensorineural Research

Description

This thyroid peroxidase mutant is useful for studies related to thyroid hormone and thyroid function. Homozygotes have dysplastic thyroid glands, severe proportional dwarfing, and delayed cochlear development with severe hearing deficit due to a lack of thyroid hormone production.

Detailed description

Mice homozygous for the teeny 2 Jackson mutation are proportional dwarfs, distinctly smaller than their heterozygous siblings. This is evident by one week of age. These mutants are severely hypothyroid with undetectable levels of T4 at 5 to 8 weeks of age. The thyroid glands are dysplastic with poorly developed follicles and hyperproliferation of epithelial cells. Although no defects have been found in the eyes, these mutants have highly elevated ABR thresholds at 4 weeks of age, the earliest age assessed, indicative of severe hearing impairment. The cochlear development is delayed and, although the cochlea resembles a normal cochlea by 1 month of age, the tectorial membrane remains abnormally thickened. Homozygotes fail to breed.

Development

The teeny 2 Jackson mutation arose spontaneously at The Jackson Laboratory in a congenic strain in which H2^g7 had been backcrossed onto the C57BL/6J host background. This mutant subline was maintained by sibling intercrossing, homozygous for H2^g7 and segregating for teeny 2 Jackson, for several years and then by backcrossing to C57BL/6J, breeding out the H2^g7. This strain reached generation N6 in 2014.

Allele

Symbol: Tpo^tee-2J
Name: teeny 2 Jackson
MGI accession ID: MGI:3721538
Generation method: Spontaneous
Marker symbol: Tpo
Marker name: thyroid peroxidase
Chromosome: 12
Strain of origin: B6.NOD-H2^g7
Molecular note: This spontaneous 64 base pair deletion includes the last 35 base pairs of exon 5 and the first 29 base pairs of intron 5, which includes the 5 prime splice donor site, and yields no normal transcript and two abnormal transcripts: a 740 bp transcript skipping only exon 5, which is predicted to causes a frame shift resulting in 12 incorrect amino acid substitutions beginning at residue 111 then a premature stop codon; and a 588 bp transcript skipping exons 4 and 5, which is predicted to delete 95 amino acids, residues 61-155.