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.
Dr. Douglas Forrest, National Institutes of Health
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
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Targeted (Null/Knockout) | Thra | thyroid hormone receptor alpha |
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 QTend 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.
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 Name | targeted mutation 1, Bjorn Vennstrom |
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Allele Type | Targeted (Null/Knockout) |
Allele Synonym(s) | TRalpha1 -; TRalpha1 KO |
Gene Symbol and Name | Thra, thyroid hormone receptor alpha |
Gene Synonym(s) | |
Strain of Origin | 129P2/OlaHsd |
Chromosome | 11 |
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. |
Mutations Made By | Dr. Bjorn Vennstrom, Karolinska Institute |
While maintaining a live colony, these mice can be maintained by mating homozygote siblings.
When using the TRα1- mouse strain in a publication, please cite the originating article(s) and include JAX stock #003461 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Thra<tm1Ven> |
Frozen Mouse Embryo | B6.129P2(C)-Thra<tm1Ven>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129P2(C)-Thra<tm1Ven>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.129P2(C)-Thra<tm1Ven>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.129P2(C)-Thra<tm1Ven>/J Frozen Embryo | $3373.50 |
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.
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