JAX Mouse Strain Datasheet - 003255

B6;129-Plp1^tm1Kan/J

Stock No:: 003255 |; PLP KO

Targeted Mutation

Cryo Recovery

Overview

Also Known As: PLP KO

These Plp1 knock-out mice exhibit no sign of motor deficits, tremors or seizures, in contrast to most naturally occurring PLP mutants.

Donating Investigator

Dr. Klaus-Armin Nave, Max-Planck-Institute of Experimental Med

Genetic overview

Genetic Background	Generation

Plp1^tm1Kan

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Plp1	proteolipid protein (myelin) 1

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Research Applications

Cancer Research
Cell Biology Research
Developmental Biology Research
Neurobiology Research

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

The gene for myelin proteolipid protein (Plp) lies on the X chromosome. Mice homozygous or hemizygous for the Plp^tm1Kan 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, Plp^tm1Kan mice do not exhibit this dysmyelination. Some ultrastructural differences are observed in the myelin of Plp^tm1Kan 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. Plp^tm1Kan mutant mice show no evidence of myelin breakdown with age.

Selected References

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: J:38856

View All References

Genetics

Plp1^tm1Kan

Allele Symbol: Plp1^tm1Kan

Allele Name	targeted mutation 1, Klaus-Armin Nave
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	PLP-null; PLP/DM20 null; Plp-
Gene Symbol and Name	Plp1, proteolipid protein (myelin) 1
Gene Synonym(s)	DM20; GPM6C; HLD1; MMPL; PLP; PLP/DM20; PMD; Plp; Plp; SPG2; jimpy; jp; msd; myelin synthesis deficiency; proteolipid protein (myelin); rsh; rump shaker
Strain of Origin	(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Chromosome	X
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.
Mutations Made By	Dr. Klaus-Armin Nave, Max-Planck-Institute of Experimental Med

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Genotype: Plp1^tm1Kan 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

Mammalian Phenotype Terms by Genotype

Genotype: Plp1^tm1Kan/Y
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system phenotype

abnormal axon morphology
- swollen axons are seen

abnormal myelin sheath morphology
- however, in non swollen regions sheaths are of normal thickness
- some attenuated myelin sheaths are seen around swollen axons

axon degeneration
- 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
- at 8 months of age occasional degenerating fibers are seen in the cervical region of the fasciculus gracilis

behavior/neurological phenotype

ataxia
- gait ataxia is seen by 18 months of age

paraparesis
- weakness particularly of the hind limbs develops by 18 months of age

Genotype: Plp1^tm1Kan/Y
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system phenotype

abnormal myelin sheath morphology
- 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
- 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

axonal spheroids
- in mice over 2 months of age, some axonal spheroids

behavior/neurological phenotype

behavior/neurological phenotype
- no signs of motor dysfunction or impaired coordination are detected

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

Genotype: Plp1^tm1Kan/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

Genotype: Plp1^tm1Kan/Y
involves: 129S1/Sv * 129X1/SvJ

nervous system phenotype

abnormal axon morphology
- after 1 year, axonal degeneration is seen in the optic nerve and fasciculus gracilis; however, no signs of peripheral neuropathy are seen
- 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
- by 1 year, numerous large axonal swellings are seen in the optic nerve and spinal cord with some also seen in Purkinje cell axons

abnormal microglial cell morphology
- increased numbers of microglia accompany degenerative changes

abnormal myelin sheath morphology
- decrease in cholesterol content
- in areas of axonal swelling the myelin sheath becomes attenuated and is eventually lost though slippage

abnormal oligodendrocyte morphology
- in primary glial cultures oligodendrocyte sheets appear larger, vacuolated, and broken suggesting decreased stability of the myelin sheet
- occasionally inner tongue processes of pligdendrocytes contain degenerated organelles
- 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

astrocytosis
- mild astrocytosis accompanies degenerative changes

demyelination
- evidence of demyelination is seen at 22 months of age

behavior/neurological phenotype

abnormal gait
- older mice develop a slow gait

abnormal locomotor coordination
- at 16 months of age impaired performance in a rotarod test is seen

impaired coordination
- at 16 months of age impaired performance in a rotarod test is seen

hematopoietic system phenotype

abnormal microglial cell morphology
- increased numbers of microglia accompany degenerative changes

immune system phenotype

abnormal microglial cell morphology
- increased numbers of microglia accompany degenerative changes

homeostasis/metabolism phenotype

decreased cholesterol level
- in myelin

Genotype: Plp1^tm1Kan/Y
B6.129-Plp1^tm1Kan

nervous system phenotype

astrocytosis
- mild astrogliosis in the hippocampal fimbria

axon degeneration
- density of axons shows a striking reduction to fewer than half that of controls

axonal spheroids

demyelination
- moderately dysmyelinated due to diminished myelination of axons with the smallest calibers, significant at 40 weeks of age

microgliosis
- low grade in the hippocampal fimbria

behavior/neurological phenotype

hindlimb paralysis
- at 40 weeks of age

growth/size/body region phenotype

decreased body weight
- at 4 and 40 weeks of age

skeleton phenotype

kyphosis
- at 40 weeks of age

immune system phenotype

microgliosis
- low grade in the hippocampal fimbria

hematopoietic system phenotype

microgliosis
- low grade in the hippocampal fimbria

Genotype: Plp1^tm1Kan/Y
B6N.129-Plp1^tm1Kan

nervous system phenotype

axonal spheroids

dysmyelination
- hypomyelination with split myelin lamellae

tomacula

References

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: 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: 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: J:48031

Additional - Plp1^tm1Kan 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: 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: 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: 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: 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: 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: 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: 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: J:31051
Harlow DE; Saul KE; Komuro H; Macklin WB. 2015. Myelin Proteolipid Protein Complexes with alphav Integrin and AMPA Receptors In Vivo and Regulates AMPA-Dependent Oligodendrocyte Progenitor Cell Migration through the Modulation of Cell-Surface GluR2 Expression. J Neurosci 35(34):12018-32. PubMed: 26311781 MGI: J:226168
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: J:156106
Mita S; de Monasterio-Schrader P; Funfschilling U; Kawasaki T; Mizuno H; Iwasato T; Nave KA; Werner HB; Hirata T. 2015. Transcallosal Projections Require Glycoprotein M6-Dependent Neurite Growth and Guidance. Cereb Cortex 25(11):4111-25. PubMed: 24917275 MGI: J:236770
Patzig J; Erwig MS; Tenzer S; Kusch K; Dibaj P; Mobius W; Goebbels S; Schaeren-Wiemers N; Nave KA; Werner HB. 2016. Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction. Elife 5:. PubMed: 27504968 MGI: J:236408
Patzig J; Kusch K; Fledrich R; Eichel MA; Luders KA; Mobius W; Sereda MW; Nave KA; Martini R; Werner HB. 2015. Proteolipid protein modulates preservation of peripheral axons and premature death when myelin protein zero is lacking. Glia :. PubMed: 26393339 MGI: J:226848
Petit B; Giraudet F; Bechon C; Bardin L; Avan P; Boespflug-Tanguy O; Begou M. 2014. Mice with a deletion of the major central myelin protein exhibit hypersensitivity to noxious thermal stimuli: involvement of central sensitization. Neurobiol Dis 65:55-68. PubMed: 24423646 MGI: J:211607
Rosenbluth J; Nave KA; Mierzwa A; Schiff R. 2006. Subtle myelin defects in PLP-null mice. Glia 54(3):172-82. PubMed: 16802387 MGI: 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: 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: 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: 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: 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: 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: 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: 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: J:201143

Service	Genotype	Price
	X linked - Homozygous Females and Hemizygous males for Plp1<tm1Kan>

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Also Known As: PLP KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Selected References

Plp1tm1Kan

Allele Symbol: Plp1tm1Kan

Disease Terms

Research Areas By Genotype

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

Genotype: Plp1tm1Kan related

Mammalian Phenotype Terms by Genotype

Genotype: Plp1tm1Kan/Yinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system phenotype

behavior/neurological phenotype

Genotype: Plp1tm1Kan/Yinvolves: 129S1/Sv * 129X1/SvJ * C57BL/6J

nervous system phenotype

behavior/neurological phenotype

Genotype: Plp1tm1Kan/Plp1+involves: 129S1/Sv * 129X1/SvJ

nervous system phenotype

Genotype: Plp1tm1Kan/Yinvolves: 129S1/Sv * 129X1/SvJ

nervous system phenotype

behavior/neurological phenotype

hematopoietic system phenotype

immune system phenotype

homeostasis/metabolism phenotype

Genotype: Plp1tm1Kan/YB6.129-Plp1tm1Kan

nervous system phenotype

behavior/neurological phenotype

growth/size/body region phenotype

skeleton phenotype

immune system phenotype

hematopoietic system phenotype

Genotype: Plp1tm1Kan/YB6N.129-Plp1tm1Kan

nervous system phenotype

References

Additional References

Additional - Plp1tm1Kan related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Plp1^tm1Kan

Allele Symbol: Plp1^tm1Kan

Genotype: Plp1^tm1Kan related

Genotype: Plp1^tm1Kan/Y
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Genotype: Plp1^tm1Kan/Y
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Genotype: Plp1^tm1Kan/Plp1⁺
involves: 129S1/Sv * 129X1/SvJ

Genotype: Plp1^tm1Kan/Y
involves: 129S1/Sv * 129X1/SvJ

Genotype: Plp1^tm1Kan/Y
B6.129-Plp1^tm1Kan

Genotype: Plp1^tm1Kan/Y
B6N.129-Plp1^tm1Kan

Additional - Plp1^tm1Kan related