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) Mating System Heterozygote x Wild-type         (Female x Male) Species laboratory mouse Background Strain C57BL/6J Donor Strain DBA/2J Generation N41F22 (10-DEC-07)

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)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Charcot-Marie-Tooth Disease, Demyelinating, Type 1A; CMT1A - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Pmp22^Tr-J/Pmp22⁺

        involves: C57BL/6

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

Pmp22^Tr-J/Pmp22^Tr-J

        involves: C57BL/6

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

Pmp22^Tr-J/?

        involves: C57BL/6

• nervous system phenotype
• abnormal Schwann cell morphology (MGI Ref ID J:7222)
  • Schwann cells are delayed or fail to ensheath axons as in wild-type mice
• abnormal myelination (MGI Ref ID J:7222)
  • 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
• behavior/neurological phenotype
• abnormal gait (MGI Ref ID J:7222)
  • mice exhibit milder gait abnormalities than in Pmp22^Tr mice
• tremors (MGI Ref ID J:7222)
  • beginning at P20 to P25

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, Type 1A

Neurobiology Research
Myelination Defects
Tremor Defects
Vestibular and Hearing Defects

Sensorineural Research
Vestibular and Hearing Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Pmp22Tr-J
Allele Name		trembler Jackson
Allele Type		Spontaneous
Common Name(s)		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; MGC20769; 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

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

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]

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]

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]

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           FGB27

Colony Maintenance

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

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Mouse Mutant Resource collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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