Tor1aflox/flox mice possess loxP sites flanking exons 3-5 of the Tor1a gene, making this stain useful for studying 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) |
Tor1aflox/flox mice possess loxP sites flanking exons 3-5 of the torsin family 1, member A (torsin A) (Tor1a) gene. TOR1A is an ATPases Associated with diverse Activities (AAA+) protein residing in the lumen of the ER/nuclear envelope (ER/NE) space. An in-frame deletion (ΔE) 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. Mice that are homozygous for this floxed allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 3-5 deleted in the cre-expressing tissues.
For example, when this floxed line is bred to B6.Cg-Tg(Nes-cre)1Kln/J mice (Stock No. 003771),cre-mediated recombination in the central and peripheral nervous system results in nestin conditional KO offspring (nestin-Cre;Tor1aflox/- or N-CKO) with abnormal motor behavior, selective areas of neurodegeneration in the central nervous system, and death by P10.
This line can be used in conjunction with mice carrying a ΔE allele (Stock No. 025637) and B6.Cg-Tg(Nes-cre)1Kln/J mice (Stock No. 003771) to generate the first viable model of primary dystonia with overt twisting movements similar to those seen in the human disease; these animals also exhibit selective areas of neurodegeneration in discrete sensorimotor structures. To generate such nestin selective knock-in mice ("N-SKI"), this line and Stock No. 003771 are first intercrossed to generate animals with one floxed Tor1a allele and the nestin-Cre transgene. These animals are subsequently crossed to this line carrying the ΔE allele (Stock No. 25637) to yield N-SKI Tor1aflox/ΔE Cre+ animals.
A targeting vector was designed to insert a loxP site upstream of exon 3 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. The construct was electroporated into (129S6/SvEvTac x C57BL/6J)F1-derived D2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with ROSA26-FLPe transgenic mice on a congenic C57BL/6J background to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene. These Tor1aflox/flox mice were maintained on a mixed background. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
Allele Name | targeted mutation 3.1, William T Dauer |
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Allele Type | Targeted (Conditional ready (e.g. floxed), No functional change) |
Allele Synonym(s) | Tor1aflox |
Gene Symbol and Name | Tor1a, torsin family 1, member A (torsin A) |
Gene Synonym(s) | |
Strain of Origin | (129S6/SvEvTac x C57BL/6J)F1 |
Chromosome | 2 |
Molecular Note | A targeting vector was designed to insert a loxP site upstream of exon 3 followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 5 of the gene. Flpe-mediated recombination removed the FRT-flanked neomycin cassette leaving exons 3-5 floxed. |
When maintaining a live colony, homozygous mice may be bred together.
When using the B6;129-Tor1atm3.1Wtd/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #025832 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Tor1a<tm3.1Wtd> |
Frozen Mouse Embryo | B6;129-Tor1a<tm3.1Wtd>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129-Tor1a<tm3.1Wtd>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129-Tor1a<tm3.1Wtd>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;129-Tor1a<tm3.1Wtd>/J Frozen Embryo | $3373.50 |
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