B6.Cg-Pmp22^Tr-J Krt25^Re/+ +/J

Stock number: 000568
Research areas: Dermatology Research, Mouse/Human Gene Homologs, Neurobiology Research

Description

These mice carry two linked, spontaneous mutations, trembler-Jackson (Pmp22^Tr-J) and rex (Krt25^Re). They are characterized by becoming progressively disabled with inability to walk and right themselves. The rex mutation is characterized by curly whiskers and wavy coats.

Detailed description

Mice heterozygous for the trembler-Jackson spontaneous mutation (Pmp22^Tr-J) are similar to heterozygotes carrying the original trembler mutation (Pmp22^Tr). However, the behavior and neuropathology of trembler-Jackson heterozygotes is less severe. The tremor phenotype cannot be reliably recognized before 20 to 25 days. There are no obvious seizures and only a mild gait abnormality. In the PNS, the myelin deficiency is considerably less severe than that of trembler mice. Homozygous trembler-Jackson mice are recognizable by 8 days of age after which they become progressively disabled. Homozygous mutant mice are unable to walk normally and can right themselves only with great difficulty; most are dead by 18 days. It should be noted that although trembler homozygotes are more severely demyelinated than trembler-Jackson homozygotes, the trembler mice live a normal lifespan while trembler-Jackson mice die prior to weaning. Survival of trembler homozygotes suggests that peripheral myelin is not essential for survival. The PNS is nearly devoid of myelin with myelinogenesis blocked in the promyelin stage. Schwann cells ensheathe individual axons but without formation of compact myelin. This C57BL/6 congenic strain is also carrying the dominant rex spontaneous mutation (Krt25^Re) that is also located on Chromosome 11.

Development

The trembler Jackson mutation arose spontaneously in the DBA/2J inbred strain at The Jackson Laboratory in 1967. This dominant mutation was maintained by backcrossing to C57BL/6J, reaching N14 in 1976. A female heterozygote was then bred to a male homozygous for rex (Krt25^Re) and heterozygous for varitant waddler Jackson (Mcoln3^Va-J) and Danforth?s short tail (Sd) in repulsion (a stock that became the C57BL/6ByJ congenic Stock #000126). The Sd/+ Pmp22^Tr-J +/+ Krt25^Re offspring were backcrossed to a B6.D2-Pmp22^Tr-J congenic heterozgyote and offspring were selected that lacked Sd and carried a recombined Chromosome 11 with Pmp22^Tr-J and Krt25^Re in coupling. This double mutant was backcrossed repeatedly to C57BL/6J and C57BL/6JEi, reaching N3 in 1978. In 1984 embryos were cryopreserved from C57BL/6J males bred to backcross generation N19 females that were either heterozygous for both Pmp22^Tr-J and Krt25^Re in coupling or wildtype for Krt25 and heterozygous for Pmp22^Tr-J, due to recombination in the previous backcross. Krt25 and Pmp22 are approximately 24 cM apart on Chromosome 11.

Allele

Symbol: Krt25^Re
Name: rex
MGI accession ID: MGI:1856137
Generation method: Spontaneous
Marker symbol: Krt25
Marker name: keratin 25
Chromosome: 11
Strain of origin: Outbred
Molecular note: This allele contains a nucleotide substitution that results in an amino acid substitution of proline for leucine at position 381 (L381P).

Allele

Symbol: Pmp22^Tr-J
Name: trembler Jackson
MGI accession ID: MGI:1856217
Generation method: Spontaneous
Marker symbol: Pmp22
Marker name: peripheral myelin protein 22
Chromosome: 11
Strain of origin: C57BL/6J
Molecular note: Sequence analysis of cDNA showed a T-to-C transition at coding nucleotide 47 resulting in the substitution of a leucine residue by a proline residue at position 16 (p.L16P).