B6.129P2(C)-Thra^tm1Ven/J

Stock number: 003461
Product name: TRα1-
Research areas: Cardiovascular Research, Internal/Organ Research, Metabolism Research

Description

These Thra knock-out mice exhibit an abnormal heart rate and lower body temperature than that of control animals. They are suitable for use in applications related to the study of hypothyroidism and cardiac function.

Detailed description

The Thra gene encodes the T3 receptor TRa1 (alpha 1) and a non-T3 bindng product TRa2 (alpha 2), generated by alternative splicing in the C-terminal region. This Thra mutant is deleted for the T3 receptor TRa1 (ALPHA ONE) but retains TRa2. These mutants have an average heart rate 20% lower than that of control animals, prolonged QT_end and QRS durations, body temperatures 0.5 degrees C lower than that of control animals. A mild hypothyrodism is present but is restricted to males.

Development

A targeting vector containing a neomycin resistance gene was used to disrupt sequence specific to the TRalpha1 alternative transcript of the targeted gene. The TRalpha2 alternative transcript is still expressed. The targeting construct was introduced into 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts to obtain chimeric animals. The resulting mice were bred to BALB/c females and then backcrossed to C57BL/6J for nine generations before the donating investigator crossed the line to an unspecified Thrb mutant line on a mostly C57BL/6 background. Mice homozygous for only the Thra mutation were generated and males sent to The Jackson Laboratory, where they were backcrossed to C57BL/6J once more.

Allele

Symbol: Thra^tm1Ven
Name: targeted mutation 1, Bjorn Vennstrom
MGI accession ID: MGI:1860441
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Thra
Marker name: thyroid hormone receptor alpha
Chromosome: 11
Strain of origin: 129P2/OlaHsd
Molecular note: A gene targeting construct was designed to disrupt the alpha1 isoform, while maintaining the integrity of the alpha2 isoform, as well as the of the orphan hormone receptor rev-erbAalpha that is transcribed on the opposite strand. RT-PCR was used to confirm these results.