Tor1aswap mutant mice possess loxP sites flanking exon 5 of the Tor1a gene, and also contains a downstream mutant exon 5. Removal of the floxed wild type exons allows expression of the mutant exon 5. This strain may be useful for studying the autosomal dominant disorder, DYT1 dystonia.
William Dauer, University of Michigan Medical School
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted (Conditional ready (e.g. floxed), No functional change) | Tor1a | torsin family 1, member A (torsin A) |
Tor1aswap mutant mice possess loxP sites flanking exon 5 of the torsin family 1, member A (torsin A) Tor1a gene. They also contain a downstream mutant exon 5 with a ΔE knockin. Tor1a is an ATPases Associated with diverse Activities (AAA+) protein residing in the lumen of the ER/nuclear envelope (ER/NE) space. The in-frame ΔE deletion in TOR1A has been shown to cause the autosomal dominant disorder, DYT1 dystonia, which is characterized by abnormal, involuntary twisting movements and muscle contractions due to selective dysfunction of CNS motor circuits. Tor1aswap mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have wildtype exon 5 deleted, and will instead express the ΔE knockin in the cre-expressing tissues.
When mice are generated carrying one Tor1aswap allele, one Tor1aflox allele (from Stock No. 025832) and Cre from B6.Cg-Tg(Nes-cre)1Kln/J mice (from Stock No. 003771), they shoe reduced survival and surviving animals show decreased growth rate adn selective degeneration of CNS motor circuits. A similar phenotype is present in homozygous induced- ΔE KI mice with cre from Stock No. 003771. The increased dosage of torsin A in these animals suppresses the lack of function mediated growth deficiency but does not supress motor abnormalities.
A targeting vector was designed by Dr. William Dauer (University of Michigan) to insert a loxP site upstream of exon 5 followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 5 of the torsin family 1, member A (torsin A) (Tor1a) gene. A mutant exon 5, with a glutamic acid residue deletion, was inserted downstream of the neo cassette. This results in a ΔE knockin shown to cause the autosomal dominant disorder, DYT1 dystonia. The construct was electroporated into B6/129SvEv embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with Flp transgenic mice to delete the neo cassette. Resulting progeny were crossed to remove the Flp-expressing transgene, and Tor1aswap offspring were maintained on a mixed B6;129 background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).
Allele Name | targeted mutation 4.1, William T Dauer |
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Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
Allele Synonym(s) | Tor1aswap |
Gene Symbol and Name | Tor1a, torsin family 1, member A (torsin A) |
Gene Synonym(s) | |
Strain of Origin | 129S/SvEv x C57BL/6 |
Chromosome | 2 |
Molecular Note | A targeting vector was designed to insert a loxP site upstream of exon 5 followed by a FRT-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 5 of the gene. A mutant exon 5, with a glutamic acid residue deletion, was inserted downstream of the neo cassette. Flp-mediated recombination removed the FRT-flanked neo cassette. |
When maintaining a live colony, homozygous mice may be bred together.
When using the Tor1aswap mouse strain in a publication, please cite the originating article(s) and include JAX stock #028099 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Tor1a<tm4.1Wtd> |
Frozen Mouse Embryo | STOCK Tor1a<tm4.1Wtd>/J | $2595.00 |
Frozen Mouse Embryo | STOCK Tor1a<tm4.1Wtd>/J | $2595.00 |
Frozen Mouse Embryo | STOCK Tor1a<tm4.1Wtd>/J | $3373.50 |
Frozen Mouse Embryo | STOCK Tor1a<tm4.1Wtd>/J | $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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