Strain Name:

B6;129-Plp1tm1Kan/J

Stock Number:

003255

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names B6;129-Plptm1Kan/J    (Changed: 05-JAN-05 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
 
Donating InvestigatorDr. Klaus-Armin Nave,   Max-Planck-Institute of Experimental Med

Description
The gene for myelin proteolipid protein (Plp) lies on the X chromosome. Mice homozygous or hemizygous for the Plptm1Kan targeted mutation are viable and fertile. Although they lack expression of the PLP protein, they show no sign of motor deficits, tremors or seizures, in contrast to most naturally occurring PLP mutants. PLP is a major membrane component of CNS myelin, and many PLP mutants show defects in myelin sheath formation. However, Plptm1Kan mice do not exhibit this dysmyelination. Some ultrastructural differences are observed in the myelin of Plptm1Kan mutant mice when compared to controls, including a less distinct difference between the major dense line (MDL) and the intraperiod line (IPL), which corresponds to reduced physical stability of the myelin sheath and suggests a function of PLP in maintenance of myelin architecture. Plptm1Kan mutant mice show no evidence of myelin breakdown with age.

Related Strains

Strains carrying other alleles of Plp1
005975   B6.Cg-Tg(Plp1-cre/ERT)3Pop/J
000287   B6CBACa Aw-J/A-Plp1jp EdaTa/J
024701   D2.Cg-Tg(Plp1-cre/ERT)3Pop/SjJ
View Strains carrying other alleles of Plp1     (3 strains)

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).
Pelizaeus-Merzbacher Disease; PMD
Spastic Paraplegia 2, X-Linked; SPG2
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Plp1tm1Kan/Y

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
  • nervous system phenotype
  • abnormal myelin sheath morphology
    • myelin is compacted but the distinction between major dense lines and intraperiod lines is less than in wild-type; however, the proportion of myelinated axons, myelin sheath thickness and size range of myelinated fibers are similar to wild-type   (MGI Ref ID J:38856)
    • in a few areas double intraperiod lines are seen and myelin sheaths are more susceptible to damage during the fixation process compared to wild-type   (MGI Ref ID J:38856)
  • axonal spheroids
    • in mice over 2 months of age, some axonal spheroids   (MGI Ref ID J:38856)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • no signs of motor dysfunction or impaired coordination are detected   (MGI Ref ID J:38856)

Plp1tm1Kan/Y

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6
  • nervous system phenotype
  • abnormal axon morphology
    • swollen axons are seen   (MGI Ref ID J:146665)
    • abnormal myelin sheath morphology
      • some attenuated myelin sheaths are seen around swollen axons   (MGI Ref ID J:146665)
      • however, in non swollen regions sheaths are of normal thickness   (MGI Ref ID J:146665)
  • axon degeneration
    • at 8 months of age occasional degenerating fibers are seen in the cervical region of the fasciculus gracilis   (MGI Ref ID J:146665)
    • at 18 months of age pronounced axonal degeneration is seen in the cervical segments in the thoracic region but not in the lumbar dorsal columns   (MGI Ref ID J:146665)
  • behavior/neurological phenotype
  • ataxia
    • gait ataxia is seen by 18 months of age   (MGI Ref ID J:146665)
  • paraparesis
    • weakness particularly of the hind limbs develops by 18 months of age   (MGI Ref ID J:146665)

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Plp1tm1Kan/Plp1+

        involves: 129S1/Sv * 129X1/SvJ
  • nervous system phenotype
  • abnormal axon morphology
    • axonal swelling and degeneration are seen but less frequently than in hemizygous males; however all optic nerve axons have normal myelin sheaths   (MGI Ref ID J:48031)

Plp1tm1Kan/Y

        involves: 129S1/Sv * 129X1/SvJ
  • nervous system phenotype
  • abnormal axon morphology
    • at 6 - 8 weeks, focal axonal swellings containing organelles are seen mostly in areas where small diameter axons predominate throughout the white and gray matter   (MGI Ref ID J:48031)
    • by 1 year, numerous large axonal swellings are seen in the optic nerve and spinal cord with some also seen in Purkinje cell axons   (MGI Ref ID J:48031)
    • after 1 year, axonal degeneration is seen in the optic nerve and fasciculus gracilis; however, no signs of peripheral neuropathy are seen   (MGI Ref ID J:48031)
    • abnormal myelin sheath morphology
      • in areas of axonal swelling the myelin sheath becomes attenuated and is eventually lost though slippage   (MGI Ref ID J:48031)
      • decrease in cholesterol content   (MGI Ref ID J:193310)
  • abnormal microglial cell morphology
    • increased numbers of microglia accompany degenerative changes   (MGI Ref ID J:48031)
  • abnormal oligodendrocyte morphology
    • occasionally inner tongue processes of pligdendrocytes contain degenerated organelles   (MGI Ref ID J:48031)
    • primary glial cultures have increased numbers of oligodendrocytes starting at the second division and persisting through at least the fourteenth division; however no increase in oligodendrocyte proliferation is seen   (MGI Ref ID J:106182)
    • in primary glial cultures oligodendrocyte sheets appear larger, vacuolated, and broken suggesting decreased stability of the myelin sheet   (MGI Ref ID J:106182)
  • astrocytosis
    • mild astrocytosis accompanies degenerative changes   (MGI Ref ID J:48031)
  • demyelination
    • evidence of demyelination is seen at 22 months of age   (MGI Ref ID J:48031)
  • behavior/neurological phenotype
  • abnormal locomotor coordination
    • at 16 months of age impaired performance in a rotarod test is seen   (MGI Ref ID J:48031)
    • abnormal gait
      • older mice develop a slow gait   (MGI Ref ID J:48031)
  • impaired coordination
    • at 16 months of age impaired performance in a rotarod test is seen   (MGI Ref ID J:48031)
  • hematopoietic system phenotype
  • abnormal microglial cell morphology
    • increased numbers of microglia accompany degenerative changes   (MGI Ref ID J:48031)
  • immune system phenotype
  • abnormal microglial cell morphology
    • increased numbers of microglia accompany degenerative changes   (MGI Ref ID J:48031)
  • homeostasis/metabolism phenotype
  • decreased cholesterol level

Plp1tm1Kan/Y

        B6.129-Plp1tm1Kan
  • nervous system phenotype
  • astrocytosis
    • mild astrogliosis in the hippocampal fimbria   (MGI Ref ID J:201143)
  • axon degeneration
    • density of axons shows a striking reduction to fewer than half that of controls   (MGI Ref ID J:201143)
    • axonal spheroids   (MGI Ref ID J:201143)
  • demyelination
    • moderately dysmyelinated due to diminished myelination of axons with the smallest calibers, significant at 40 weeks of age   (MGI Ref ID J:201143)
  • microgliosis
    • low grade in the hippocampal fimbria   (MGI Ref ID J:201143)
  • behavior/neurological phenotype
  • hindlimb paralysis
    • at 40 weeks of age   (MGI Ref ID J:201143)
  • growth/size/body phenotype
  • decreased body weight
    • at 4 and 40 weeks of age   (MGI Ref ID J:201143)
  • skeleton phenotype
  • kyphosis
    • at 40 weeks of age   (MGI Ref ID J:201143)
  • immune system phenotype
  • microgliosis
    • low grade in the hippocampal fimbria   (MGI Ref ID J:201143)
  • hematopoietic system phenotype
  • microgliosis
    • low grade in the hippocampal fimbria   (MGI Ref ID J:201143)
View Research Applications

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

Plp1tm1Kan related

Cancer Research
Genes Regulating Growth and Proliferation

Cell Biology Research
Genes Regulating Growth and Proliferation

Developmental Biology Research
Embryonic Lethality (Homozygous)
Neurodevelopmental Defects
Postnatal Lethality
      Homozygous

Neurobiology Research
Myelination Defects
Neurodevelopmental Defects
Neurotrophic Factor Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Plp1tm1Kan
Allele Name targeted mutation 1, Klaus-Armin Nave
Allele Type Targeted (Null/Knockout)
Common Name(s) PLP-null; PLP/DM20 null; Plp-;
Mutation Made ByDr. Klaus-Armin Nave,   Max-Planck-Institute of Experimental Med
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Plp1, proteolipid protein (myelin) 1
Chromosome X
Gene Common Name(s) DM20; GPM6C; HLD1; MMPL; PLP; PLP/DM20; PMD; Plp; SPG2; jimpy; jp; msd; myelin synthesis deficiency; proteolipid protein (myelin); rsh; rump shaker;
Molecular Note A neomycin resistance cassette introduced by homologous recombination replaced the 3' part of exon 1,including the translation start codon and a 2.5 kb fragment of the first intron of Plp ("PLP/DM20 gene"). Western blot analysis showed absence of both PLP and DM20 proteolipids proteins in hemizygous mutant mice. [MGI Ref ID J:38856]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Klugmann M; Schwab MH; Puhlhofer A; Schneider A; Zimmermann F ; Griffiths IR ; Nave KA. 1997. Assembly of CNS myelin in the absence of proteolipid protein. Neuron 18(1):59-70. [PubMed: 9010205]  [MGI Ref ID J:38856]

Additional References

Edgar JM; Anderson TJ; Dickinson PJ; Barrie JA; McCulloch MC; Nave KA; Griffiths IR. 2002. Survival of, and competition between, oligodendrocytes expressing different alleles of the Plp gene. J Cell Biol 158(4):719-29. [PubMed: 12177040]  [MGI Ref ID J:78727]

Griffiths I; Klugmann M; Anderson T; Yool D; Thomson C; Schwab MH ; Schneider A ; Zimmermann F ; McCulloch M ; Nadon N ; Nave KA. 1998. Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 280(5369):1610-3. [PubMed: 9616125]  [MGI Ref ID J:48031]

Plp1tm1Kan related

Chow E; Mottahedeh J; Prins M; Ridder W; Nusinowitz S; Bronstein JM. 2005. Disrupted compaction of CNS myelin in an OSP/Claudin-11 and PLP/DM20 double knockout mouse. Mol Cell Neurosci 29(3):405-13. [PubMed: 15886014]  [MGI Ref ID J:99981]

Coetzee T; Suzuki K; Nave KA; Popko B. 1999. Myelination in the absence of galactolipids and proteolipid proteins. Mol Cell Neurosci 14(1):41-51. [PubMed: 10433816]  [MGI Ref ID J:57688]

Edgar JM; Anderson TJ; Dickinson PJ; Barrie JA; McCulloch MC; Nave KA; Griffiths IR. 2002. Survival of, and competition between, oligodendrocytes expressing different alleles of the Plp gene. J Cell Biol 158(4):719-29. [PubMed: 12177040]  [MGI Ref ID J:78727]

Edgar JM; McLaughlin M; Werner HB; McCulloch MC; Barrie JA; Brown A; Faichney AB; Snaidero N; Nave KA; Griffiths IR. 2009. Early ultrastructural defects of axons and axon-glia junctions in mice lacking expression of Cnp1. Glia 57(16):1815-24. [PubMed: 19459211]  [MGI Ref ID J:156196]

Edgar JM; McLaughlin M; Yool D; Zhang SC; Fowler JH; Montague P; Barrie JA; McCulloch MC; Duncan ID; Garbern J; Nave KA; Griffiths IR. 2004. Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia. J Cell Biol 166(1):121-31. [PubMed: 15226307]  [MGI Ref ID J:146664]

Garbern JY; Yool DA; Moore GJ; Wilds IB; Faulk MW; Klugmann M; Nave KA; Sistermans EA; van der Knaap MS; Bird TD; Shy ME; Kamholz JA; Griffiths IR. 2002. Patients lacking the major CNS myelin protein, proteolipid protein 1, develop length-dependent axonal degeneration in the absence of demyelination and inflammation. Brain 125(Pt 3):551-61. [PubMed: 11872612]  [MGI Ref ID J:146665]

Griffiths I; Klugmann M; Anderson T; Yool D; Thomson C; Schwab MH ; Schneider A ; Zimmermann F ; McCulloch M ; Nadon N ; Nave KA. 1998. Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science 280(5369):1610-3. [PubMed: 9616125]  [MGI Ref ID J:48031]

Griffiths IR; Schneider A; Anderson J; Nave KA. 1995. Transgenic and natural mouse models of proteolipid protein (PLP)-related dysmyelination and demyelination. Brain Pathol 5(3):275-81. [PubMed: 8520727]  [MGI Ref ID J:31051]

Karim SA; Barrie JA; McCulloch MC; Montague P; Edgar JM; Kirkham D; Anderson TJ; Nave KA; Griffiths IR; McLaughlin M. 2007. PLP overexpression perturbs myelin protein composition and myelination in a mouse model of Pelizaeus-Merzbacher disease. Glia 55(4):341-51. [PubMed: 17133418]  [MGI Ref ID J:156106]

Rosenbluth J; Nave KA; Mierzwa A; Schiff R. 2006. Subtle myelin defects in PLP-null mice. Glia 54(3):172-82. [PubMed: 16802387]  [MGI Ref ID J:156122]

Rosenbluth J; Schiff R; Lam P. 2009. Effects of osmolality on PLP-null myelin structure: implications re axon damage. Brain Res 1253:191-7. [PubMed: 19094971]  [MGI Ref ID J:147791]

Skoff RP; Bessert DA; Cerghet M; Franklin MJ; Rout UK; Nave KA; Carlock L; Ghandour MS; Armant DR. 2004. The myelin proteolipid protein gene modulates apoptosis in neural and non-neural tissues. Cell Death Differ 11(12):1247-57. [PubMed: 15375385]  [MGI Ref ID J:115458]

Skoff RP; Saluja I; Bessert D; Yang X. 2004. Analyses of proteolipid protein mutants show levels of proteolipid protein regulate oligodendrocyte number and cell death in vitro and in vivo. Neurochem Res 29(11):2095-103. [PubMed: 15662843]  [MGI Ref ID J:106182]

Werner HB; Kramer-Albers EM; Strenzke N; Saher G; Tenzer S; Ohno-Iwashita Y; De Monasterio-Schrader P; Mobius W; Moser T; Griffiths IR; Nave KA. 2013. A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system. Glia 61(4):567-86. [PubMed: 23322581]  [MGI Ref ID J:193310]

Werner HB; Kuhlmann K; Shen S; Uecker M; Schardt A; Dimova K; Orfaniotou F; Dhaunchak A; Brinkmann BG; Mobius W; Guarente L; Casaccia-Bonnefil P; Jahn O; Nave KA. 2007. Proteolipid protein is required for transport of sirtuin 2 into CNS myelin. J Neurosci 27(29):7717-30. [PubMed: 17634366]  [MGI Ref ID J:145263]

Yin X; Baek RC; Kirschner DA; Peterson A; Fujii Y; Nave KA; Macklin WB; Trapp BD. 2006. Evolution of a neuroprotective function of central nervous system myelin. J Cell Biol 172(3):469-78. [PubMed: 16449196]  [MGI Ref ID J:105721]

Yin X; Kidd GJ; Nave KA; Trapp BD. 2008. P0 protein is required for and can induce formation of schmidt-lantermann incisures in myelin internodes. J Neurosci 28(28):7068-73. [PubMed: 18614675]  [MGI Ref ID J:137961]

de Monasterio-Schrader P; Patzig J; Mobius W; Barrette B; Wagner TL; Kusch K; Edgar JM; Brophy PJ; Werner HB. 2013. Uncoupling of neuroinflammation from axonal degeneration in mice lacking the myelin protein tetraspanin-2. Glia 61(11):1832-47. [PubMed: 24038504]  [MGI Ref ID J:201143]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3300.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $4290.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We willfulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

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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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