Mice that are homozygous for this Tbce, tubulin-specific chaperone e, spontaneous mutation, pmn, are viable but die prematurely. Onset of progressive atrophy and paralysis occurs at 2 to 3 weeks of age. Homozygotes die by 6 to 7 weeks of age due to respiratory failure. Neurodegeneration starts in the motor endplates, progresses to loss of axons and results in apoptosis of the cell bodies. This mutant mouse strain may be useful in studies of Spinal Muscular Atrohpy, muscular atrophy, motor neuronopathy and neurodegeneration.
Michael Sendtner, University of Wuerzburg
Mice that are homozygous for this spontaneous mutation are viable but die prematurely. Onset of locomotor impairment with corresponding motor neuron and muscular degeneration occurs at 2 to 3 weeks of age. Atrophy and paralysis starts in the hind limbs and pelvic girdle and is progressive. Homozygotes die by 6 to 7 weeks of age due to respiratory failure. Neurodegeneration starts in the motor endplates, progresses to loss of axons and results in apoptosis of the cell bodies. Electrophysiological deficiencies are detected by 13 days of age, before the neurodegeneration is clinically visible. Electron microscopic analysis of sciatic and phrenic nerves reveals a reduced number of microtubules. TBCE protein is destabilized, producing a reduction in tubulin and microtubules in motor neuron axons. Progressive microtubule loss occurs in axons distal to proximal and corresponds to axon degeneration. The mutation arose in the NMRI/Pan outbred line and has been identified as a Trp524Gly substitution (T1570G transversion) of the Tbce, tubulin-specific chaperone e, gene. Heterozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain may be useful in studies of Spinal Muscular Atrohpy, muscular atrophy, motor neuronopathy and neurodegeneration.
The mutation was first recorded at the Panum Institute (Kopenhagen, Denmark) in 1988. The mutation arose in the NMRI/Pan outbred line and has been identified as a Trp524Gly substitution of the Tbce (tubulin-specific chaperone e) gene. The donating investigator reports that these Tbcepmn mutant mice were bred onto the NMRI outbred background for 32 generations, and then Tbcepmn heterozygous males were sent to The Jackson Laboratory Repository. Upon arrival, sperm was cryopreserved from some of these Tbcepmn heterozygous mice. To rederive a living colony on the NMRI genetic background, heterozygous sperm was used to fertilize oocytes from NMRI/Gat-Tg(MGMT)3Bec/J mice (Stock No. 003076). The resulting double mutant mice will be bred together (and the Tg(MGMT)3Bec selectively bred away) to establish the Tbcepmn colony.
|Allele Name||progressive motor neuronopathy|
|Allele Synonym(s)||pmn; progressive motor neuropathy; TbceG|
|Gene Symbol and Name||Tbce, tubulin-specific chaperone E|
|Strain of Origin||NMRI/Pan|
|General Note||This mutation was identified in 1988 at the Panum Institute in Copenhagen.|
|Molecular Note||The mutation has been identified as T-to-G transversion, resulting in a p.Trp524Gly amino acid substitution in the encoded protein. Northern analysis detected no difference in transcript levels between mutant and wild-type mice. That the mutation was due a defect in Tbce was demonstrated through complementation with a line expressing a Tbce transgene.|
|Mutations Made By|| |
Michael Sendtner, University of Wuerzburg
When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes are viable but die by 6 to 7 weeks of age.
When using the NMRI-Tbcepmn/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009682 in your Materials and Methods section.
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