|These LoxSOD1G37R mice harbor a floxed transgene comprised of the human SOD1 gene bearing a G37R mutation that is causative of inherited Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease). These mice develop ALS-like fatal, progressive paralysis by 1 year of age.|
Type Congenic; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation +pN1
Donating Investigator Dr. Don Cleveland, Ludwig Institute for Cancer Res. (UCSD)
The LoxSOD1G37R transgene has loxP sites flanking a human G37R mutant superoxide dismutase 1, soluble gene sequence (SOD1*G37R) that is characterized as an enzymatically active, "gain of adverse function" mutation. SOD1 is a widely expressed isozyme responsible for destroying free superoxide radicals. SOD1 mutations, including SOD1*G37R, are known to cause Amyotrophic Lateral Sclerosis (ALS). Hemizygotes mice are viable and fertile. These mice develop symptoms and pathology resembling human ALS, including progressive weight loss from denervation-induced muscle atrophy and paralyzation. Transgenic mice develop the fatal progressive motor neuron disease and die by 12-14 months of age, with neuron death in 55% of spinal motor neurons.
When LoxSOD1G37R transgenic mice are bred to mice expressing tissue-specific Cre recombinase, the resulting offspring will have the floxed-SOD1*G37R transgene deleted in the cre-expressing tissues. When SOD1*G37R expression is deleted in microglia and myeloid cells, the progression of disease was delayed. When SOD1*G37R expression is deleted in Schwann cells, disease progression was significantly accelerated. These mice may be useful in studying SOD1 in neuromuscular disorders, including ALS or Lou Gehrig's Disease.
The SOD1*G37R transgene was designed with the entire human floxed-superoxide dismutase 1, soluble (SOD1) gene, modified to harbor the SOD1*G37R mutation, driven by its endogenous human promoter. The transgene was microinjected into fertilized (C57BL/6J x C3H/HeJ) F2 oocytes. SOD1*G37R mice from founder line 1 were backcrossed onto a C57BL/6 background for at least 30 generations (see SNP note below). Upon arrival at The Jackson Laboratory Repository, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.
|Considerations for Choosing Controls|
Amyotrophic Lateral Sclerosis (ALS)
009680 B6.B-Vps54wr/J 010700 B6.Cg-Tg(Prnp-TARDBP*A315T)95Balo/J 002298 B6.Cg-Tg(SOD1)2Gur/J 008229 B6.Cg-Tg(SOD1*G37R)29Dpr/J 008342 B6.Cg-Tg(SOD1*G37R)42Dpr/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 018917 B6;SJL-Tg(Prnp-CCS)17Jlel/J 026406 B6;SJL-Tg(Prnp-FUS*R521C)3313Ejh/J 020783 B6J.Cg-Tg(Prnp-FUS)17Ljh/J 021459 B6J.Cg-Tg(Prnp-FUS*H517Q)29Ljh/J 019728 B6J.Cg-Tg(Prnp-FUS*R495X)78Ljh/J 021572 B6J.Cg-Tg(Prnp-FUS*R521G)2Ljh/J 017907 B6N.Cg-Tg(Prnp-TARDBP)96Dwc/J 017933 B6N.Cg-Tg(Prnp-TARDBP*Q331K)103Dwc/J 017930 B6N.Cg-Tg(Prnp-TARDBP*Q331K)109Dwc/J 025402 B6SJL-Tg(Prnp-Immt/SOD1)1Gmnf/J 025403 B6SJL-Tg(Prnp-Immt/SOD1*G93A)7Gmnf/J 016201 B6SJL-Tg(Prnp-TARDBP)4Jlel/J 002297 B6SJL-Tg(SOD1)2Gur/J 002726 B6SJL-Tg(SOD1*G93A)1Gur/J 002300 B6SJL-Tg(SOD1*G93A)dl1Gur/J 016608 C57BL/6-Tg(Prnp-TARDBP)3cPtrc/J 017604 C57BL/6-Tg(Prnp-TARDBP*M337V)4Ptrc/J 002628 C57BL/6-Tg(SOD1)10Cje/J 002629 C57BL/6-Tg(SOD1)3Cje/J 005706 C57BL/6-Tg(tetO-CDK5R1/GFP)337Lht/J 023088 C57BL/6J-Tg(C9orf72_i2)8Lutzy/J 023099 C57BL/6J-Tg(C9orf72_i3)112Lutzy/J 008230 FVB(Cg)-Tg(Thy1-SOD1*G93A)T3Hgrd/J 005110 FVB-Tg(Sod1*G86R)M1Jwg/J 013199 FVB.Cg-Tg(SOD1*G93A)1Gur/J 013574 FVB/N-Tg(149m19)M141Kunst/J 017919 STOCK Tg(CAG-EGFP,-dsRed2/RNAi:Tardbp)6Zxu/J 017934 STOCK Tg(CAG-dsRed2/RNAi:Tardbp)6Zxu/J 017916 STOCK Tg(Prnp-FUS)WT3Cshw/J 016144 STOCK Tg(Prnp-TARDBP)4Jlel/J 016143 STOCK Tg(Prnp-TARDBP*A315T)23Jlel/JView Amyotrophic Lateral Sclerosis (ALS) (39 strains)Strains carrying other alleles of SOD1
017458 B6(C)-Tg(UAS-EGFP,-SOD1*G37R)135Gsn/J 017460 B6(C)-Tg(UAS-EGFP,-SOD1*G37R)677Gsn/J 002298 B6.Cg-Tg(SOD1)2Gur/J 008229 B6.Cg-Tg(SOD1*G37R)29Dpr/J 008342 B6.Cg-Tg(SOD1*G37R)42Dpr/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 025402 B6SJL-Tg(Prnp-Immt/SOD1)1Gmnf/J 025403 B6SJL-Tg(Prnp-Immt/SOD1*G93A)7Gmnf/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 013199 FVB.Cg-Tg(SOD1*G93A)1Gur/JView Strains carrying other alleles of SOD1 (17 strains)
View Related Disease (OMIM) TermsRelated Disease (OMIM) Terms provided by MGI
- Potential model based on transgenic expression of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested.View Mammalian Phenotype TermsMammalian Phenotype Terms provided by MGIassigned by genotype
- premature death
- transgenic mice develop end-stage disease by 8.5-11 months of age (MGI Ref ID J:109131)
- growth/size/body phenotype
- weight loss
- mice display weight loss from denervation induced muscle atrophy (MGI Ref ID J:109131)
- nervous system phenotype
- decreased motor neuron number
- mice in end-stage disease display 55% spinal motor neuron death (MGI Ref ID J:109131)
- motor neuron degeneration
- mice develop fatal progressive motorneuron disease (MGI Ref ID J:109131)View Research Applications
|Allele Name||transgene insertion 1, Don W Cleveland|
|Allele Type||Transgenic (Conditional ready (e.g. floxed), Humanized sequence, Inserted expressed sequence)|
|Mutation Made By||Dr. Don 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|
|General Note||Mice develop fatal progressive motorneuron disease, including weight loss from denervation-induced muscle atrophy and paralysis. The highest expressing line reached end stage disease between 8.5 and 11 months. No human SOD1 was expressed in progeny from transgenic females that also expressed a germ line Cre transgene. The effects of mutant SOD1 within motorneurons was assessed by mating human mutant SOD1-expressing transgenic mice with mice expressing Cre under control of the Islet-1 promoter to remove expression from motorneurons specifically.|
|Molecular Note||The SOD1*G37R transgene was designed with the entire human "floxed"-superoxide dismutase 1, soluble (SOD1) gene, modified to harbor the SOD1*G37R mutation, driven by its endogenous human promoter. The expressed protein is characterized as an enzymatically active, "gain of adverse function" mutation. When transgenic mice are bred to mice expressing tissue-specific Cre recombinase, the resulting offspring will have the floxed-SOD1*G37R sequence deleted in the cre-expressing tissues. [MGI Ref ID J:109131]|
Boillee S; Yamanaka K; Lobsiger CS; Copeland NG; Jenkins NA; Kassiotis G; Kollias G; Cleveland DW. 2006. Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia. Science 312(5778):1389-92. [PubMed: 16741123] [MGI Ref ID J:109131]
Chang Y; Kong Q; Shan X; Tian G; Ilieva H; Cleveland DW; Rothstein JD; Borchelt DR; Wong PC; Lin CL. 2008. Messenger RNA oxidation occurs early in disease pathogenesis and promotes motor neuron degeneration in ALS. PLoS ONE 3(8):e2849. [PubMed: 18682740] [MGI Ref ID J:140123]
Da Cruz S; Parone PA; Lopes VS; Lillo C; McAlonis-Downes M; Lee SK; Vetto AP; Petrosyan S; Marsala M; Murphy AN; Williams DS; Spiegelman BM; Cleveland DW. 2012. Elevated PGC-1alpha activity sustains mitochondrial biogenesis and muscle function without extending survival in a mouse model of inherited ALS. Cell Metab 15(5):778-86. [PubMed: 22560226] [MGI Ref ID J:184777]
Furukawa Y; Kaneko K; Yamanaka K; O'Halloran TV; Nukina N. 2008. Complete loss of post-translational modifications triggers fibrillar aggregation of SOD1 in the familial form of amyotrophic lateral sclerosis. J Biol Chem 283(35):24167-76. [PubMed: 18552350] [MGI Ref ID J:140373]
Kang SH; Li Y; Fukaya M; Lorenzini I; Cleveland DW; Ostrow LW; Rothstein JD; Bergles DE. 2013. Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis. Nat Neurosci 16(5):571-9. [PubMed: 23542689] [MGI Ref ID J:197615]
Lobsiger CS; Boillee S; McAlonis-Downes M; Khan AM; Feltri ML; Yamanaka K; Cleveland DW. 2009. Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice. Proc Natl Acad Sci U S A 106(11):4465-70. [PubMed: 19251638] [MGI Ref ID J:146766]
Mishra A; Maheshwari M; Chhangani D; Fujimori-Tonou N; Endo F; Joshi AP; Jana NR; Yamanaka K. 2013. E6-AP association promotes SOD1 aggresomes degradation and suppresses toxicity. Neurobiol Aging 34(4):1310.e11-23. [PubMed: 23040663] [MGI Ref ID J:203386]
Parone PA; Da Cruz S; Han JS; McAlonis-Downes M; Vetto AP; Lee SK; Tseng E; Cleveland DW. 2013. Enhancing mitochondrial calcium buffering capacity reduces aggregation of misfolded SOD1 and motor neuron cell death without extending survival in mouse models of inherited amyotrophic lateral sclerosis. J Neurosci 33(11):4657-71. [PubMed: 23486940] [MGI Ref ID J:196358]
Yamanaka K; Chun SJ; Boillee S; Fujimori-Tonou N; Yamashita H; Gutmann DH; Takahashi R; Misawa H; Cleveland DW. 2008. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nat Neurosci 11(3):251-3. [PubMed: 18246065] [MGI Ref ID J:135268]
Zhong Z; Ilieva H; Hallagan L; Bell R; Singh I; Paquette N; Thiyagarajan M; Deane R; Fernandez JA; Lane S; Zlokovic AB; Liu T; Griffin JH; Chow N; Castellino FJ; Stojanovic K; Cleveland DW; Zlokovic BV. 2009. Activated protein C therapy slows ALS-like disease in mice by transcriptionally inhibiting SOD1 in motor neurons and microglia cells. J Clin Invest 119(11):3437-49. [PubMed: 19841542] [MGI Ref ID J:154597]
Animal Health ReportsProduction of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) mice from the colony or to C57BL/6NJ inbred mice (Stock No. 005304)
|Pricing for USA, Canada and Mexico shipping destinations|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2140.00
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.
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 will fulfill 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|
Cryopreserved Mice - Ready for Recovery
Price (US dollars $) Cryorecovery* $2782.00
Cryorecovery - Standard.
Progeny testing is not required.
|Considerations for Choosing Controls|
|Control Pricing Information for Genetically Engineered Mutant Strains.|
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