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Type Mutant Stock; Targeted Mutation; Mating System +/+ sibling x Heterozygote (Female x Male) Species laboratory mouse Generation ?+N1F4 (25-APR-08) Donating Investigator William Dauer, Columbia University Description
Homozygous mutant mice have a perinatal lethal phenotype. They fail to feed or vocalize at birth, and typically die within 48 hours. No protein is detected by immunoblot analysis in tissues (liver, brain, spinal cord, mouse embryonic fibroblasts (MEFs)) from homozygous mutant animals. Microscopic and ultrastructural examination of central nervous system neurons from embryonic day 18 homozygous embryos reveals abnormalities including dysmorphic ventral horn neuron nuclei, vesicles in the neuronal nuclear envelope and enlarged endoplasmic reticulum. Neurons within homozygotes appear normal when migrating, but develop nuclear membrane abnormalities upon maturation.In contrast to homozygous mutant mice, heterozygotes are viable, fertile, normal in size, and do not manifest any gross physical or behavioral abnormalities. Torsin A (TOR1A) protein levels in heterozygous mice are approximately 50% of wildtype levels. This mutant mouse strain may be useful in studies of torsion dystonia 1 and neurodevelopment.
Development
A targeting vector containing a loxP site flanked neomycin resistance gene and phosphoglycerine kinase promoter and an IRES-tau and lacZ cassette was used to disrupt exons 2, 3 and 4. The construct was electroporated into 129S1/SvImJ derived W9.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to mice expressing Cre recombinase (129.Cg-Tg(Hsp70-1-cre)1Arge), to remove the PGK-neo selection cassette.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
Mammalian Phenotype Terms assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Tor1atm1Wtd/Tor1a+
involves: 129S1/Sv
- cellular phenotype
- abnormal nucleus morphology (MGI Ref ID J:107596)
- nuclear envelope morphology is normal compared to Tor1a homozygous or compound mutants
Tor1atm1Wtd/Tor1atm1Wtd
involves: 129S1/Sv
- lethality-prenatal/perinatal
- prenatal lethality (MGI Ref ID J:107596)
- homozygotes typically die within 48 hours after birth
- cellular phenotype
- abnormal nucleus morphology (MGI Ref ID J:107596)
- lumen of the nuclear envelope contains large numbers of vesicles that appear to derive from the inner nuclear membrane with ventral horn neurons most severely affected
- nuclear envelope abnormalities are observed in neurons in the spinal cord, pons, frontal cortex and hippocampus; ventral horn neurons in mutants have an abnormal nuclear shape, being abnormally convoluted compared to wild-type neurons
- behavior/neurological phenotype
- abnormal suckling behavior (MGI Ref ID J:107596)
- homozygous pups fail to feed after birth
- abnormal vocalization (MGI Ref ID J:107596)
- homozygous pups do not vocalize after birth
- nervous system phenotype
- abnormal spinal cord morphology (MGI Ref ID J:107596)
- membrane abnormalities are more severe in the ventral spinal cord compared to the dorsal spinal cord at E18.5
Research Applications
This mouse can be used to support research in many areas including:
Cell Biology Research
Developmental Biology Research
Neurodevelopmental Defects
Perinatal Lethality (Homozygous)
| Allele Symbol | Tor1atm1Wtd | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, William T Dauer | ||
| Common Name(s) | Tor1a-; | ||
| Mutation Made By | William Dauer, Columbia University | ||
| Strain of Origin | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| ES Cell Line Name | W9.5/W95 | ||
| ES Cell Line Strain | 129S1/Sv-Oca2<+> Tyr<+> Kitl<+> | ||
| Gene Symbol and Name | Tor1a, torsin family 1, member A (torsin A) | ||
| Chromosome | 2 | ||
| Gene Common Name(s) | DQ2; DYT1; Dyt1; dystonia 1; torsin family 1, member A; torsinA; | ||
| Molecular Note | An IRES-lacZ cassette replaced exons 2-4, which contain sequence encoding the conserved AAA+ ATP binding and hydrolysis domains. A neomycin resistance gene included in the vector was subsequently removed via cre mediated recombination. [MGI Ref ID J:107596] | ||
Genotyping Protocols
Tor1atm1Wtd, , vers. 1
Tor1atm1Wtd, SEP PCR, vers. 2
Helpful Links
Optimizing PCR Protocols
Tor1atm1Wtd related
Goodchild RE; Kim CE; Dauer WT. 2005. Loss of the dystonia-associated protein torsinA selectively disrupts the neuronal nuclear envelope. Neuron 48(6):923-32. [PubMed: 16364897] [MGI Ref ID J:107596]
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, these mice are bred as heterozygotes. Homozygotes have a perinatal lethal phenotype. Diet Information LabDiet® 5K52/5K67
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $236.40 Female or Male Heterozygous for Tor1atm1Wtd *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $288.65 Heterozygous for Tor1atm1Wtd x Wild-type for Tor1atm1Wtd $288.65 Wild-type for Tor1atm1Wtd x Heterozygous for Tor1atm1Wtd
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $307.40 Female or Male Heterozygous for Tor1atm1Wtd *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $375.30 Heterozygous for Tor1atm1Wtd x Wild-type for Tor1atm1Wtd $375.30 Wild-type for Tor1atm1Wtd x Heterozygous for Tor1atm1Wtd
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Effective September 26, 2007: License Requirements for Strains using Cre-lox Technology only apply in Canada, see Licenses for Strains using Cre-lox Technology.
For additional Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.
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