Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N10 (24-JUN-08)   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)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      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 (MGI Ref ID J:18407)
  • 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
  • the cytoplasmic leaflet of the periaxonal membrane is often fused with the inner compact myelin lamellae to form a dense line
  • when present, the cytoplasm of the periaxonal collar is usually disorganized
• behavior/neurological phenotype
• abnormal grooming behavior (MGI Ref ID J:18407)
  • less frequent exploratory sniffing and grooming on a bar-cross apparatus
• hypoactivity (MGI Ref ID J:18407)
  • show decreased locomotor activity on a bar-cross apparatus
• impaired coordination (MGI Ref ID J:18407)
  • slower to transverse a narrow challenge bar
• tremors (MGI Ref ID J:18407)
  • many homozygotes exhibit a mild, transient, trunk tremor on a bar-cross apparatus

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

Allele Symbol		Magtm1Rod
Allele Name		targeted mutation 1, John Roder
Allele Type		Targeted (knock-out)
Mutation Made By		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, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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

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]

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]

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]

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]

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]

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; 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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, homozygous mice are bred.
Mating System	Homozygote x Homozygote         (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 Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
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

See Terms of Use

The Jackson Laboratory's Genotype Promise

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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

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General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
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Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

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