C57BL/6J-Pmp22^Tr-2J/GrsrJ

Stock number: 021550
Research areas: Neurobiology Research, Reproductive Biology Research, Sensorineural Research

Description

This comparatively mild point mutation in the second transmembrane domain provides an excellent model for Dejerine-Sottas syndrome, Roussy-Levy syndrome, recurrent neuropathy with pressure palsies, and types 1A and 1E Charcot-Marie-Tooth disease.

Detailed description

Trembler 2 Jackson heterozygotes can be identified by approximately 3 weeks of age by a rapid tremor and unsteady, wobbly gait. They have spasticity in the muscles of the lower back and limbs and reduced ability to organize the hind limb movements. These phenotypes derive from peripheral demyelination. Although heterozygotes for this allele have not been found to die prematurely, male fertility is reduced. Some, but not all, heterozygotes have elevated auditory brainstem responses. This allele causes a less severe phenotype than the trembler mutation, with no paralysis, seizures, or juvenile mortality.

Development

The trembler 2 Jackson mutation arose spontaneously in 2012 in a C57BL/6J mutant subline that had a spontaneous mutation in a gene on Chromosome 1. Genotyping confirmed that the Chromosome 1 mutation was absent from this new mutant subline. The trembler 2 Jackson mutation has been maintained by continuous backcross of heterozygous females with C57BL/6J males. In 2013 this coisogenic strain reached N3.

Allele

Symbol: Pmp22^Tr-2J
Name: trembler 2 Jackson
MGI accession ID: MGI:5515890
Generation method: Spontaneous
Marker symbol: Pmp22
Marker name: peripheral myelin protein 22
Marker synonyms: CIDP; CMT1A; CMT1E; DSS; GAS3; GAS-3; HMSNIA; HNPP; Sp110; TRE002
Chromosome: 11
Strain of origin: C57BL/6J
Molecular note: This spontaneous C-to-A transversion on chromosome 11 position 6,3151,168 (GRCm38) changes a codon in exon 4 and causes a serine to arginine substitution at amino acid 76 (p.S76R), which is in the second transmembrane domain.