Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+N1F4pN1 Generation Definitions   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 Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Additional Web Information

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Dystonia 1, Torsion, Autosomal Dominant; DYT1   (TOR1A)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Tor1a^tm1Wtd/Tor1a⁺

        involves: 129S1/Sv

• cellular phenotype
• abnormal cell nucleus morphology
  • nuclear envelope morphology is normal compared to Tor1a homozygous or compound mutants   (MGI Ref ID J:107596)

Tor1a^tm1Wtd/Tor1a^tm1Wtd

        involves: 129S1/Sv

• mortality/aging
• complete neonatal lethality
  • homozygotes typically die within 48 hours after birth   (MGI Ref ID J:107596)
• cellular phenotype
• abnormal cell nucleus morphology
  • 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   (MGI Ref ID J:107596)
  • 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   (MGI Ref ID J:107596)
• behavior/neurological phenotype
• abnormal suckling behavior
  • homozygous pups fail to feed after birth   (MGI Ref ID J:107596)
• abnormal vocalization
  • homozygous pups do not vocalize after birth   (MGI Ref ID J:107596)
• nervous system phenotype
• abnormal spinal cord morphology
  • membrane abnormalities are more severe in the ventral spinal cord compared to the dorsal spinal cord at E18.5   (MGI Ref ID J:107596)

View Research Applications

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

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Tor1atm1Wtd
Allele Name		targeted mutation 1, William T Dauer
Allele Type		Targeted (knock-out)
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

Genotyping Information

Genotyping Protocols

Tor1a^tm1Wtd, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Tor1a^tm1Wtd 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]

Kim CE; Perez A; Perkins G; Ellisman MH; Dauer WT. 2010. A molecular mechanism underlying the neural-specific defect in torsinA mutant mice. Proc Natl Acad Sci U S A 107(21):9861-6. [PubMed: 20457914]  [MGI Ref ID J:160544]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as heterozygotes. Homozygotes have a perinatal lethal phenotype.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

The Jackson Laboratory's Genotype Promise

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.

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