Description

Strain Information

Type Congenic; Mutant Strain; Spontaneous Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Wild-type x Heterozygote         (Female x Male)   05-DEC-08 Mating System Heterozygote x Wild-type         (Female x Male)   05-DEC-08 Species laboratory mouse Background Strain C57BL/6J Donor Strain DBA/2J Generation [N41F28p]+N1F3 (21-DEC-12) Generation Definitions

Appearance
black, tremors
Related Genotype: a/a Pmp22^Tr-J/+

black, unaffected
Related Genotype: a/a +/+

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.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying   Pmp22^Tr-J allele

000568

B6.Cg-Pmp22Tr-J Krt25Re/+ +/J

View Strains carrying   Pmp22^Tr-J     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Charcot-Marie-Tooth Disease, Demyelinating, Type 1A; CMT1A

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Charcot-Marie-Tooth Disease and Deafness   (PMP22) Guillain-Barre Syndrome, Familial; GBS   (PMP22) Hypertrophic Neuropathy of Dejerine-Sottas   (PMP22) Neuropathy, Hereditary, with Liability to Pressure Palsies; HNPP   (PMP22) Roussy-Levy Hereditary Areflexic Dystasia   (PMP22)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Pmp22^Tr-J/Pmp22⁺

        involves: C57BL/6

• nervous system phenotype
• abnormal Schwann cell morphology
  • Schwann cell nuclei numbers are increased   (MGI Ref ID J:39953)
  • Shwann cell numbers and rates of apoptosis are increased compared to in wild-type mice   (MGI Ref ID J:134811)
  • however, treatment with curcumin decreases apoptosis rates of Schwann cells   (MGI Ref ID J:134811)
• abnormal axon morphology
  • treatment with curcumin increases axonal size   (MGI Ref ID J:134811)
• abnormal dorsal root ganglion morphology
  • mice exhibit minor structural changes in dorsal root ganglion cells   (MGI Ref ID J:39953)
• abnormal myelination   (MGI Ref ID J:98231)
  • 40% to 60% of axons lack myelination   (MGI Ref ID J:39953)
• behavior/neurological phenotype
• abnormal gait
  • beginning at 4 to 6 weeks of age, mice exhibit abnormal gait with hindlimb spaying   (MGI Ref ID J:39953)
• impaired coordination
  • mice are unable to remain on a rotarod as long as wild-type mice   (MGI Ref ID J:134811)
  • however, treatment with curcumin improves coordination   (MGI Ref ID J:134811)
• muscle phenotype
• muscle degeneration
  • mice exhibit muscle wasting   (MGI Ref ID J:39953)

Pmp22^Tr-J/Pmp22^Tr-J

        involves: C57BL/6

• mortality/aging
• decreased survivor rate
  • most mice die by day 18   (MGI Ref ID J:7945)
• postnatal lethality
  • most mice die by day 18   (MGI Ref ID J:7945)
• behavior/neurological phenotype
• abnormal motor coordination/ balance
  • mice are noticeably disabled at day 8 and progressively worsen such that they have a difficult time walking   (MGI Ref ID J:7945)

Pmp22^Tr-J/?

        involves: C57BL/6

• nervous system phenotype
• abnormal Schwann cell morphology
  • Schwann cells are delayed or fail to ensheath axons as in wild-type mice   (MGI Ref ID J:7222)
• abnormal myelination
  • mice exhibit mild deficiencies in myelin at the sciatic and vagus nerves compared to in wild-type but not as severe as in Pmp22^Tr mice   (MGI Ref ID J:7222)
• behavior/neurological phenotype
• abnormal gait
  • mice exhibit milder gait abnormalities than in Pmp22^Tr mice   (MGI Ref ID J:7222)
• tremors
  • beginning at P20 to P25   (MGI Ref ID J:7222)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Pmp22^Tr-J related

Mouse/Human Gene Homologs
Charcot-Marie-Tooth disease

Neurobiology Research
Myelination Defects
Tremor Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Pmp22Tr-J
Allele Name		trembler Jackson
Allele Type		Spontaneous
Common Name(s)		TrJ; TrJ; trembler-j;
Strain of Origin		C57BL/6J
Gene Symbol and Name		Pmp22, peripheral myelin protein 22
Chromosome		11
Gene Common Name(s)		CMT1A; CMT1E; DSS; GAS-3; Gas-3; HMSNIA; HNPP; Sp110; Tr; growth arrest specific 3; trembler;
Molecular Note		Sequence analysis of cDNA showed a T to C transition at nucleotide position 47 resulting in the substitution of a leucine residue by a proline residue. [MGI Ref ID J:1058] [MGI Ref ID J:3394]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Henry EW; Cowen JS; Sidman RL. 1983. Comparison of Trembler and Trembler-J mouse phenotypes: varying severity of peripheral hypomyelination. J Neuropathol Exp Neurol 42(6):688-706. [PubMed: 6313869]  [MGI Ref ID J:7222]

Suter U; Moskow JJ; Welcher AA; Snipes GJ; Kosaras B; Sidman RL; Buchberg AM; Shooter EM. 1992. A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse. Proc Natl Acad Sci U S A 89(10):4382-6. [PubMed: 1374899]  [MGI Ref ID J:1058]

Pmp22^Tr-J related

Bolin LM; McNeil T; Lucian LA; DeVaux B; Franz-Bacon K; Gorman DM; Zurawski S; Murray R; McClanahan TK. 1997. HNMP-1: a novel hematopoietic and neural membrane protein differentially regulated in neural development and injury. J Neurosci 17(14):5493-502. [PubMed: 9204931]  [MGI Ref ID J:49822]

Coulpier F; Decker L; Funalot B; Vallat JM; Garcia-Bragado F; Charnay P; Topilko P. 2010. CNS/PNS boundary transgression by central glia in the absence of Schwann cells or Krox20/Egr2 function. J Neurosci 30(17):5958-67. [PubMed: 20427655]  [MGI Ref ID J:159829]

Devaux JJ; Scherer SS. 2005. Altered ion channels in an animal model of Charcot-Marie-Tooth disease type IA. J Neurosci 25(6):1470-80. [PubMed: 15703401]  [MGI Ref ID J:98231]

Ewaleifoh O; Trinh M; Griffin JW; Nguyen T. 2012. A novel system to accelerate the progression of nerve degeneration in transgenic mouse models of neuropathies. Exp Neurol 237(1):153-9. [PubMed: 22688009]  [MGI Ref ID J:187069]

Fortun J; Li J; Go J; Fenstermaker A; Fletcher BS; Notterpek L. 2005. Impaired proteasome activity and accumulation of ubiquitinated substrates in a hereditary neuropathy model. J Neurochem 92(6):1531-41. [PubMed: 15748170]  [MGI Ref ID J:97015]

Fortun J; Verrier JD; Go JC; Madorsky I; Dunn WA; Notterpek L. 2007. The formation of peripheral myelin protein 22 aggregates is hindered by the enhancement of autophagy and expression of cytoplasmic chaperones. Neurobiol Dis 25(2):252-65. [PubMed: 17174099]  [MGI Ref ID J:119095]

Henry EW; Cowen JS; Sidman RL. 1983. Comparison of Trembler and Trembler-J mouse phenotypes: varying severity of peripheral hypomyelination. J Neuropathol Exp Neurol 42(6):688-706. [PubMed: 6313869]  [MGI Ref ID J:7222]

Henry EW; Sidman RL. 1983. The murine mutation trembler-J: proof of semidominant expression by use of the linked vestigial tail marker. J Neurogenet 1(1):39-52. [PubMed: 6681440]  [MGI Ref ID J:7945]

Khajavi M; Shiga K; Wiszniewski W; He F; Shaw CA; Yan J; Wensel TG; Snipes GJ; Lupski JR. 2007. Oral curcumin mitigates the clinical and neuropathologic phenotype of the Trembler-J mouse: a potential therapy for inherited neuropathy. Am J Hum Genet 81(3):438-53. [PubMed: 17701891]  [MGI Ref ID J:134811]

Kosaras B; Rosario C; Ruiz M; Sidman R; Tang M; Wertheim S. 1992. Trembler (Tr) and trembler-J (TrJ) molecular genetics Mouse Genome 90(3):421.  [MGI Ref ID J:2533]

Lupski JR; Garcia CA. 1992. Molecular genetics and neuropathology of Charcot-Marie-Tooth disease type 1A. Brain Pathol 2(4):337-49. [PubMed: 1341967]  [MGI Ref ID J:13351]

Meekins GD; Emery MJ; Weiss MD. 2004. Nerve conduction abnormalities in the trembler-j mouse: a model for Charcot-Marie-Tooth disease type 1A? J Peripher Nerv Syst 9(3):177-82. [PubMed: 15363066]  [MGI Ref ID J:101812]

Misko A; Ferguson T; Notterpek L. 2002. Matrix metalloproteinase mediated degradation of basement membrane proteins in Trembler J neuropathy nerves. J Neurochem 83(4):885-94. [PubMed: 12421361]  [MGI Ref ID J:80088]

Notterpek L; Shooter EM; Snipes GJ. 1997. Upregulation of the endosomal-lysosomal pathway in the trembler-J neuropathy. J Neurosci 17(11):4190-200. [PubMed: 9151736]  [MGI Ref ID J:40430]

Nunn DJ; Robertson HA; Peterson MR. 1983. Elevated benzodiazepine receptor density in forebrain of the mutant mouse trembler (TrJ). Exp Neurol 82(1):245-7. [PubMed: 6313422]  [MGI Ref ID J:26981]

Robertson AM; Huxley C; King RH; Thomas PK. 1999. Development of early postnatal peripheral nerve abnormalities in Trembler-J and PMP22 transgenic mice. J Anat 195(Pt 3):331-9. [PubMed: 10580849]  [MGI Ref ID J:58582]

Robertson AM; King RH; Muddle JR; Thomas PK. 1997. Abnormal Schwann cell/axon interactions in the Trembler-J mouse. J Anat 190(Pt 3):423-32. [PubMed: 9147228]  [MGI Ref ID J:39953]

Robertson AM; Perea J; McGuigan A; King RH; Muddle JR; Gabreels-Festen AA; Thomas PK; Huxley C. 2002. Comparison of a new pmp22 transgenic mouse line with other mouse models and human patients with CMT1A. J Anat 200(4):377-90. [PubMed: 12090404]  [MGI Ref ID J:76795]

Sahenk Z; Galloway G; Edwards C; Malik V; Kaspar BK; Eagle A; Yetter B; Forgie A; Tsao D; Lin JC. 2010. TrkB and TrkC agonist antibodies improve function, electrophysiologic and pathologic features in Trembler J mice. Exp Neurol 224(2):495-506. [PubMed: 20553714]  [MGI Ref ID J:162328]

Suter U; Moskow JJ; Welcher AA; Snipes GJ; Kosaras B; Sidman RL; Buchberg AM; Shooter EM. 1992. A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse. Proc Natl Acad Sci U S A 89(10):4382-6. [PubMed: 1374899]  [MGI Ref ID J:1058]

Suter U; Nave KA. 1999. Transgenic mouse models of CMT1A and HNPP. Ann N Y Acad Sci 883:247-53. [PubMed: 10586249]  [MGI Ref ID J:59848]

Valentijn LJ; Baas F; Wolterman RA; Hoogendijk JE; van den Bosch NH; Zorn I; Gabreels-Festen AW; de Visser M; Bolhuis PA. 1992. Identical point mutations of PMP-22 in Trembler-J mouse and Charcot-Marie-Tooth disease type 1A. Nat Genet 2(4):288-91. [PubMed: 1303281]  [MGI Ref ID J:3394]

Zielasek J; Martini R; Suter U; Toyka KV. 2000. Neuromyotonia in mice with hereditary myelinopathies. Muscle Nerve 23(5):696-701. [PubMed: 10797391]  [MGI Ref ID J:113066]

Zielasek J; Toyka KV. 1999. Nerve conduction abnormalities and neuromyotonia in genetically engineered mouse models of human hereditary neuropathies. Ann N Y Acad Sci 883:310-20. [PubMed: 10586256]  [MGI Ref ID J:59844]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           FGB29

Colony Maintenance

Mating System	Wild-type x Heterozygote         (Female x Male)   05-DEC-08
	Heterozygote x Wild-type         (Female x Male)   05-DEC-08
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• View the complete collection of spontaneous mutants in the Mouse Mutant Resource.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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