Description

Strain Information

Type Congenic; Transgenic; Additional information on Genetically Engineered Mutant Mice. Mating System Noncarrier x Hemizygote         (Female x Male) Species laboratory mouse Generation N6+ (19-AUG-08)   Donating Investigator Donald Cleveland,   Ludwig Institute for Cancer Res. (UCSD)

Description
Mice hemizygous for this G37R-SOD1 transgene are viable and fertile. The expressed G37R mutant form of human SOD1 is characterized as an enzymatically active, "gain of adverse function" mutation. Hemizygotes develop symptoms and pathology resembling human Amyotrophic Lateral Sclerosis (ALS), with paralyzation in one or more limbs attributable to the loss of motor neurons from the spinal cord. Transgenic mice from the highest expressing founder line (G37R(42) or line 42) express a 14-fold increase in SOD1 activity in spinal cord with death occurring around 3.5-4 months of age. High expression of G37R-SOD1 is associated with ALS pathology in motor neurons of the spinal cord and brainstem, widespread degenerative changes in other neuronal populations, and mild-to-moderate vacuolar changes in kidney. These high-expressing G37R(42) (or G37R-SOD1 line 42) transgenic mice may be useful in studying neuromuscular disorders, including Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease).

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. As the G37R-SOD1 transgenic mice were originally created on a mixed genetic background, it should be noted that the phenotype of the congenic mice could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
The G37R-SOD1 (or SOD1-G37R) transgene was designed with a mutant human SOD1 gene (harboring a single amino acid substitution of glycine to arginine at codon 37) driven by its endogenous human promoter. This 12 kb transgene was microinjected into hybrid (C57BL/6J x C3H/HeJ)F2 mouse embryos and transgenic G37R-SOD1 mice (founder line 42) were established. These mice were then backcrossed to C57BL/6J inbred mice for many generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of SOD1

002298	B6.Cg-Tg(SOD1)2Gur/J
008248	B6.Cg-Tg(SOD1*G85R)148Dwc/J
004435	B6.Cg-Tg(SOD1*G93A)1Gur/J
002299	B6.Cg-Tg(SOD1*G93A)dl1Gur/J
002297	B6SJL-Tg(SOD1)2Gur/J
002726	B6SJL-Tg(SOD1*G93A)1Gur/J
002300	B6SJL-Tg(SOD1*G93A)dl1Gur/J
002628	C57BL/6-Tg(SOD1)10Cje/J
002629	C57BL/6-Tg(SOD1)3Cje/J
008230	FVB(Cg)-Tg(Thy1-SOD1*G93A)T3Hgrd/J

View Strains carrying other alleles of SOD1     (10 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Amyotrophic Lateral Sclerosis 1; ALS1 -

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.

Tg(SOD1*G37R)42Dpr/0

        involves: C3H/HeJ * C57BL/6J

• nervous system phenotype
• abnormal spinal cord morphology (MGI Ref ID J:69178)
  • mice exhibit vacuolization in the neutropil of substantia gelatinosa and scattered in some of the fiber tracts of the ventral and lateral white matter of the spinal cord
• decreased motor neuron number (MGI Ref ID J:69178)
  • at late stages
• motor neuron degeneration (MGI Ref ID J:69178)
  • motor neuron degeneration is observed in the ventral horns of the lumbar, thoracic, and cervical spinal cord as well as the brain stem
  • degeneration is associated with vacuole formation in both dendrites and axons of motor neurons
  • mice exhibit axonal degradation in dorsal roots of motor neurons
• brain vacuoles (MGI Ref ID J:69178)
  • in the choroid plexus
• behavior/neurological phenotype
• hindlimb paralysis (MGI Ref ID J:69178)
  • eventually mice develop hindlimb paralysis
• hypoactivity (MGI Ref ID J:69178)
  • at 3.5 to 4 months of age, mice exhibit decreased spontaneous movement compared to wild-type mice
• tremors (MGI Ref ID J:69178)
  • at 3.5 to 4 months of age, mice exhibit axial tremors
• weakness (MGI Ref ID J:69178)
  • at 3.5 to 4 months of age, mice exhibit asymmetric weakness of the limbs and when suspended by their tail exhibit difficulties extending and moving hindlimbs
• muscle phenotype
• abnormal muscle electrophysiology (MGI Ref ID J:69178)
  • mice exhibit spontaneous, positive sharp waves associated with denervation atrophy
• muscular atrophy (MGI Ref ID J:69178)
  • at 3.5 to 4 months of age, mice exhibit muscle wasting particularly along the flanks
• cellular phenotype
• abnormal mitochondrial morphology (MGI Ref ID J:69178)
  • motor neurons exhibit mitochondrial degradation
• growth/size phenotype
• weight loss (MGI Ref ID J:69178)
  • progressive
• skin/coat/nails phenotype
• rough hair (MGI Ref ID J:69178)
  • at 3.5 to 4 months of age
• renal/urinary system phenotype
• abnormal proximal convoluted tubule morphology (MGI Ref ID J:69178)
  • mice exhibit vacuolization of epithelial cells in the proximal tubules of the kidney

View Research Applications

Research Applications

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

Mouse/Human Gene Homologs
amyotrophic lateral sclerosis (ALS)

Neurobiology Research
Amyotrophic Lateral Sclerosis (ALS)
Neurodegeneration

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(SOD1*G37R)42Dpr
Allele Name		transgene insertion 42, Donald L Price
Allele Type		Transgenic (random, expressed)
Common Name(s)		G37R SOD1 line 42; G37R(42); SOD1 G37R line 42; Tg(SOD1-G37R)42Dpr;
Mutation Made By		Donald Cleveland,   Ludwig Institute for Cancer Res. (UCSD)
Strain of Origin		(C57BL/6J x C3H/HeJ)F2
Expressed Gene		SOD1, superoxide dismutase 1, soluble, human
Promoter		SOD1, superoxide dismutase 1, soluble, human
Molecular Note		A 12 kb genomic DNA fragment containing a mutated form of human SOD1 with a glycine to arginine substitution at amino acid 37 (G37R) was used for the transgene. The G37R mutation is found in some cases of familial amyotrophic lateral sclerosis (FALS). [MGI Ref ID J:69178]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(SOD1*G93A)1Gur, QPCR, vers. 2
Tg(SOD1), STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Wong PC; Pardo CA; Borchelt DR; Lee MK; Copeland NG; Jenkins NA; Sisodia SS; Cleveland DW; Price DL. 1995. An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 14(6):1105-16. [PubMed: 7605627]  [MGI Ref ID J:69178]

Additional References

Tg(SOD1*G37R)42Dpr related

Beaulieu JM; Nguyen MD; Julien JP. 1999. Late onset death of motor neurons in mice overexpressing wild-type peripherin J Cell Biol 147(3):531-44. [PubMed: 15132161]  [MGI Ref ID J:58388]

Borchelt DR; Lee MK; Slunt HS; Guarnieri M; Xu ZS; Wong PC; Brown RH Jr; Price DL; Sisodia SS; Cleveland DW. 1994. Superoxide dismutase 1 with mutations linked to familial amyotrophic lateral sclerosis possesses significant activity. Proc Natl Acad Sci U S A 91(17):8292-6. [PubMed: 8058797]  [MGI Ref ID J:133801]

Bruijn LI; Beal MF; Becher MW; Schulz JB; Wong PC; Price DL; Cleveland DW. 1997. Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant. Proc Natl Acad Sci U S A 94(14):7606-11. [PubMed: 9207139]  [MGI Ref ID J:133804]

Eyer J; Cleveland DW; Wong PC; Peterson AC. 1998. Pathogenesis of two axonopathies does not require axonal neurofilaments. Nature 391(6667):584-7. [PubMed: 9468135]  [MGI Ref ID J:91502]

Ilieva HS; Yamanaka K; Malkmus S; Kakinohana O; Yaksh T; Marsala M; Cleveland DW. 2008. Mutant dynein (Loa) triggers proprioceptive axon loss that extends survival only in the SOD1 ALS model with highest motor neuron death. Proc Natl Acad Sci U S A 105(34):12599-604. [PubMed: 18719118]  [MGI Ref ID J:138825]

Kim D; Nguyen MD; Dobbin MM; Fischer A; Sananbenesi F; Rodgers JT; Delalle I; Baur JA; Sui G; Armour SM; Puigserver P; Sinclair DA; Tsai LH. 2007. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J 26(13):3169-79. [PubMed: 17581637]  [MGI Ref ID J:133121]

Lobsiger CS; Boillee S; Cleveland DW. 2007. Toxicity from different SOD1 mutants dysregulates the complement system and the neuronal regenerative response in ALS motor neurons. Proc Natl Acad Sci U S A 104(18):7319-26. [PubMed: 17463094]  [MGI Ref ID J:133802]

Nguyen MD; Lariviere RC; Julien JP. 2001. Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofilament inclusions. Neuron 30(1):135-47. [PubMed: 11343650]  [MGI Ref ID J:69136]

Yamanaka K; Boillee S; Roberts EA; Garcia ML; McAlonis-Downes M; Mikse OR; Cleveland DW; Goldstein LS. 2008. Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice. Proc Natl Acad Sci U S A 105(21):7594-9. [PubMed: 18492803]  [MGI Ref ID J:136374]

Zhong Z; Deane R; Ali Z; Parisi M; Shapovalov Y; O'Banion MK; Stojanovic K; Sagare A; Boillee S; Cleveland DW; Zlokovic BV. 2008. ALS-causing SOD1 mutants generate vascular changes prior to motor neuron degeneration. Nat Neurosci 11(4):420-2. [PubMed: 18344992]  [MGI Ref ID J:136100]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Breeding & Husbandry	Mutant mice were bred to C57BL/6J mice to generate this congenic strain. When maintaining the live congenic colony, hemizygous carriers may be bred with wildtype siblings or C57BL/6J inbred mice.
Mating System	Noncarrier x Hemizygote         (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
	Noncarrier
	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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

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

Terms of Use

Terms of Use

General Terms and Conditions

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.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.