NMRI-Tbce^pmn/J

Stock number: 009682
Research areas: Neurobiology Research

Description

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.

Detailed description

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.

Development

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 Tbce^pmn mutant mice were bred onto the NMRI outbred background for 32 generations, and then Tbce^pmn heterozygous males were sent to The Jackson Laboratory Repository. Upon arrival, sperm was cryopreserved from some of these Tbce^pmn 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 Tbce^pmn colony.

Allele

Symbol: Tbce^pmn
Name: progressive motor neuronopathy
MGI accession ID: MGI:1856997
Generation method: Spontaneous
Synonyms: pmn; progressive motor neuropathy; Tbce^G
Marker symbol: Tbce
Marker name: tubulin-specific chaperone E
Marker synonyms: 2610206D02Rik; C530005D02Rik; HRD; KCS; KCS1; pac2; PEAMO
Chromosome: 13
Strain of origin: NMRI/Pan
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.
General note: This mutation was identified in 1988 at the Panum Institute in Copenhagen.