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

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N6+F1pN1 Generation Definitions   Donating Investigator Richard Quarles,   NINDS, NIH

Description
Mice homozygous for this targeted mutation are viable and fertile. The endogenous protein had previously been thought to be necessary for myelin formation. However in the homozygous mutant the degree of myelination and its compaction are normal. Finer motor coordination abilities are significantly affected in the homozygous mutant and they exhibit a subtle intention tremor. The organization of the periaxonal region is partially impaired with the periaxonal cytoplasmic collar frequently missing in optic nerve, cervical spinal cord, and ventral roots. Later in life, beginning at 6 months, oligodendrocytes degenerate. This strain may serve as a model for some aspects of multiple sclerosis. MAG also tranduces a signal to axons. Therefore, axons in the MAG-deficient mice are smaller in calliber due to the aberrant phosphorylation of neurofilaments. MAG has also been shown to be an inhibitor of nerve regeneration. MAG-deficient mice congenic on a C57BL/6 background may exhibit substantially more degeneration of CNS axons compared to deficiency on the original mixed background.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
The targeted mutation was created by Dr. John Roder (University of Toronto) by designing a targeting vector to insert a neomycin resistance cassette into exon 5 of the targeted gene. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. The original strain (see Stock No. 002403) on a mixed C57BL/6, 129 inbred and the CD1 outbred genetic background was sent to Dr. Richard Quarles (NINDS/NIH). There, mutant mice were backcrossed for at least 13 generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Mag^tm1Rod allele

002403

STOCK Magtm1Rod/J

View Strains carrying   Mag^tm1Rod     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Mag^tm1Rod/Mag^tm1Rod

        involves: 129S1/Sv * 129X1/SvJ

• nervous system phenotype
• abnormal axon morphology
  • optic nerve, cervical spinal cord, and ventral roots exhibit frequent loss of periaxonal cytoplasmic collar, periaxonal collar swelling, cytoplasm within myelin, and redundant myelin, however degree of myelination and its compaction are normal   (MGI Ref ID J:18407)
  • the cytoplasmic leaflet of the periaxonal membrane is often fused with the inner compact myelin lamellae to form a dense line   (MGI Ref ID J:18407)
  • when present, the cytoplasm of the periaxonal collar is usually disorganized   (MGI Ref ID J:18407)
• behavior/neurological phenotype
• abnormal grooming behavior
  • less frequent exploratory sniffing and grooming on a bar-cross apparatus   (MGI Ref ID J:18407)
• hypoactivity
  • show decreased locomotor activity on a bar-cross apparatus   (MGI Ref ID J:18407)
• impaired coordination
  • slower to transverse a narrow challenge bar   (MGI Ref ID J:18407)
• tremors
  • many homozygotes exhibit a mild, transient, trunk tremor on a bar-cross apparatus   (MGI Ref ID J:18407)

View Research Applications

Research Applications

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

Neurobiology Research
Ataxia (Movement) Defects
Myelination Defects
Tremor Defects

Research Tools
Neurobiology Research

Mag^tm1Rod related

Neurobiology Research
Myelination Defects
Tremor Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Magtm1Rod
Allele Name		targeted mutation 1, John Roder
Allele Type		Targeted (knock-out)
Mutation Made By		Dr. John Roder,   University of Toronto
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Mag, myelin-associated glycoprotein
Chromosome		7
Gene Common Name(s)		GMA; Gma; S-MAG; SIGLEC-4A; SIGLEC4A;
Molecular Note		A neomycin resistance cassette was inserted into exon 5 of the gene. Mutant mice showed a complete lack of mRNA and protein in the central nervous system for the targeted gene. Nerves from the peripheral nervous system also lacked protein for the targeted gene. [MGI Ref ID J:18407]

Genotyping

Genotyping Information

Genotyping Protocols

Mag^tm1Rod, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Li C; Tropak MB; Gerlai R; Clapoff S; Abramow-Newerly W; Trapp B; Peterson A; Roder J. 1994. Myelination in the absence of myelin-associated glycoprotein. Nature 369(6483):747-50. [PubMed: 7516497]  [MGI Ref ID J:18407]

Pan B; Fromholt SE; Hess EJ; Crawford TO; Griffin JW; Sheikh KA; Schnaar RL. 2005. Myelin-associated glycoprotein and complementary axonal ligands, gangliosides, mediate axon stability in the CNS and PNS: neuropathology and behavioral deficits in single- and double-null mice. Exp Neurol 195(1):208-17. [PubMed: 15953602]  [MGI Ref ID J:100940]

Additional References

Mag^tm1Rod related

Bai Y; Zhang X; Katona I; Saporta MA; Shy ME; O'Malley HA; Isom LL; Suter U; Li J. 2010. Conduction block in PMP22 deficiency. J Neurosci 30(2):600-8. [PubMed: 20071523]  [MGI Ref ID J:157710]

Cafferty WB; Duffy P; Huebner E; Strittmatter SM. 2010. MAG and OMgp synergize with Nogo-A to restrict axonal growth and neurological recovery after spinal cord trauma. J Neurosci 30(20):6825-37. [PubMed: 20484625]  [MGI Ref ID J:160516]

Cai Z; Sutton-Smith P; Swift J; Cash K; Finnie J; Turnley A; Thompson PD; Blumbergs PC. 2002. Tomacula in MAG-deficient mice. J Peripher Nerv Syst 7(3):181-9. [PubMed: 12365566]  [MGI Ref ID J:103883]

Dickendesher TL; Baldwin KT; Mironova YA; Koriyama Y; Raiker SJ; Askew KL; Wood A; Geoffroy CG; Zheng B; Liepmann CD; Katagiri Y; Benowitz LI; Geller HM; Giger RJ. 2012. NgR1 and NgR3 are receptors for chondroitin sulfate proteoglycans. Nat Neurosci 15(5):703-12. [PubMed: 22406547]  [MGI Ref ID J:191258]

Duffy P; Wang X; Siegel CS; Tu N; Henkemeyer M; Cafferty WB; Strittmatter SM. 2012. Myelin-derived ephrinB3 restricts axonal regeneration and recovery after adult CNS injury. Proc Natl Acad Sci U S A 109(13):5063-8. [PubMed: 22411787]  [MGI Ref ID J:182224]

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]

Fry EJ; Ho C; David S. 2007. A role for Nogo receptor in macrophage clearance from injured peripheral nerve. Neuron 53(5):649-62. [PubMed: 17329206]  [MGI Ref ID J:122959]

Haney CA; Sahenk Z; Li C; Lemmon VP; Roder J; Trapp BD. 1999. Heterophilic binding of L1 on unmyelinated sensory axons mediates Schwann cell adhesion and is required for axonal survival. J Cell Biol 146(5):1173-84. [PubMed: 10477768]  [MGI Ref ID J:57603]

Khazaei MR; Halfter H; Karimzadeh F; Koo JH; Margolis FL; Young P. 2010. Bex1 is involved in the regeneration of axons after injury. J Neurochem 115(4):910-20. [PubMed: 20731761]  [MGI Ref ID J:166463]

Kumar S; Yin X; Trapp BD; Paulaitis ME; Hoh JH. 2002. Role of long-range repulsive forces in organizing axonal neurofilament distributions: evidence from mice deficient in myelin-associated glycoprotein. J Neurosci Res 68(6):681-90. [PubMed: 12111829]  [MGI Ref ID J:104964]

Lee JK; Geoffroy CG; Chan AF; Tolentino KE; Crawford MJ; Leal MA; Kang B; Zheng B. 2010. Assessing spinal axon regeneration and sprouting in Nogo-, MAG-, and OMgp-deficient mice. Neuron 66(5):663-70. [PubMed: 20547125]  [MGI Ref ID J:163185]

Li C; Trapp B; Ludwin S; Peterson A; Roder J. 1998. Myelin associated glycoprotein modulates glia-axon contact in vivo. J Neurosci Res 51(2):210-7. [PubMed: 9469574]  [MGI Ref ID J:45616]

Lopez PH; Ahmad AS; Mehta NR; Toner M; Rowland EA; Zhang J; Dore S; Schnaar RL. 2011. Myelin-associated glycoprotein protects neurons from excitotoxicity. J Neurochem 116(5):900-8. [PubMed: 21214567]  [MGI Ref ID J:170525]

Marcus J; Dupree JL; Popko B. 2002. Myelin-associated glycoprotein and myelin galactolipids stabilize developing axo-glial interactions. J Cell Biol 156(3):567-77. [PubMed: 11827985]  [MGI Ref ID J:77227]

Nguyen T; Mehta NR; Conant K; Kim KJ; Jones M; Calabresi PA; Melli G; Hoke A; Schnaar RL; Ming GL; Song H; Keswani SC; Griffin JW. 2009. Axonal protective effects of the myelin-associated glycoprotein. J Neurosci 29(3):630-7. [PubMed: 19158290]  [MGI Ref ID J:144847]

Uschkureit T; Sporkel O; Stracke J; Bussow H; Stoffel W. 2000. Early onset of axonal degeneration in double (plp-/-mag-/-) and hypomyelinosis in triple (plp-/-mbp-/-mag-/-) mutant mice. J Neurosci 20(14):5225-33. [PubMed: 10884306]  [MGI Ref ID J:63480]

Vabnick I; Messing A; Chiu SY; Levinson SR; Schachner M; Roder J; Li C; Novakovic S; Shrager P. 1997. Sodium channel distribution in axons of hypomyelinated and MAG null mutant mice. J Neurosci Res 50(2):321-36. [PubMed: 9373041]  [MGI Ref ID J:44044]

Weiss MD; Luciano CA; Quarles RH. 2001. Nerve conduction abnormalities in aging mice deficient for myelin-associated glycoprotein. Muscle Nerve 24(10):1380-7. [PubMed: 11562920]  [MGI Ref ID J:116346]

Yin X; Crawford TO; Griffin JW; Tu P; Lee VM; Li C; Roder J; Trapp BD. 1998. Myelin-associated glycoprotein is a myelin signal that modulates the caliber of myelinated axons. J Neurosci 18(6):1953-62. [PubMed: 9482781]  [MGI Ref ID J:160879]

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]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice are bred.

Pricing and Purchasing

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Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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