B6;129-Tor1a^tm1Wtd/J

Stock number: 006251
Product name: Tor1a-
Research areas: Cell Biology Research, Developmental Biology Research

Description

Homozygous Tor1a^tm1Wtd knock-out mice exhibit abnormal development of central nervous system neurons and may be useful in studies of neurodevelopment.

Detailed 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.

Allele

Symbol: Tor1a^tm1Wtd
Name: targeted mutation 1, William T Dauer
MGI accession ID: MGI:3623421
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tor1a
Marker name: torsin family 1, member A (torsin A)
Chromosome: 2
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
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.