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| These G85R-SOD1 transgenic mice may be useful in studying neuromuscular disorders, including Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease). | |||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
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 G85R-SOD1 transgene are viable and fertile, with transgenic expression of a G85R mutant form of human SOD1 associated with human familial Amyotrophic Lateral Sclerosis (ALS). Mice from this founder line (line 148) exhibit unaltered endogenous SOD1 activity; the G85R mutation is characterized as an "enzymatically inactive" mutation. Hemizygotes develop symptoms and pathology resembling human ALS; becoming paralyzed in one or more limbs due to loss of motor neurons from the spinal cord, with disease onset and rapid progression to death between 7-8 months of age. Like wildtype SOD1, the G85R mutant SOD1 protein also forms monomer-misfolded oligomers associated with degenerating motor neurons. These G85R-SOD1 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 G85R-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 G85R-SOD1 (or SOD1-G85R) transgene was designed with a mutant human SOD1 gene (harboring a single amino acid substitution of glycine to arginine at codon 85) driven by its endogenous human promoter. This 12 kb transgene was microinjected into hybrid (C57BL/6J x C3H/HeJ)F2 mouse embryos and transgenic G85R-SOD1 mice (founder line 148) 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 008342 B6.Cg-Tg(SOD1*G37R)42Dpr/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
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*G85R)148Dwc | ||
|---|---|---|---|
| Allele Name | transgene insertion 148, Don W Cleveland | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | 148-G85R; G85R; G85R SOD1 line148; G85R line 148; SOD1 G85R line 148; Tg(SOD1-G85R)148Dwc; | ||
| Mutation Made By | Donald Cleveland, Ludwig Institute for Cancer Res. (UCSD) | ||
| Expressed Gene | SOD1, superoxide dismutase 1, soluble, human | ||
| Promoter | SOD1, superoxide dismutase 1, soluble, human | ||
| General Note | Transgenic animals initially exhibit hindlimb weakness that spreads with rapid progression to forelimbs and results in muscle atrophy and complete paralysis within 2 weeks. Founders 148-G85R and 74-G85R are the highest and lowest expressing transgenic lines, respectively, and differ in onset of clinical symptoms, presumably due to gene dosage. Founder 148-G85R exhibits muscle weakness at 8-10 months of age whereas founder 74-G85R exhibits the phenotype 12-14 months of age. Despite the difference in disease onset both founders show the same rate of disease progression after appearance of initial symptoms. | ||
| Molecular Note | A 12 kb genomic fragment of human SOD1 carrying a glycine to arginine substitution at amino acid 85 (G85R), a mutation associated with familial amyotrophic lateral sclerosis (ALS), was used as the transgene. [MGI Ref ID J:77600] | ||
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)
Bruijn LI; Becher MW; Lee MK; Anderson KL; Jenkins NA; Copeland NG; Sisodia SS; Rothstein JD; Borchelt DR; Price DL; Cleveland DW. 1997. ALS-linked SOD1 mutant G85R mediates damage to astrocytes and promotes rapidly progressive disease with SOD1-containing inclusions. Neuron 18(2):327-38. [PubMed: 9052802] [MGI Ref ID J:77600]
Additional References
Tg(SOD1*G85R)148Dwc relatedAmendola J; Verrier B; Roubertoux P; Durand J. 2004. Altered sensorimotor development in a transgenic mouse model of amyotrophic lateral sclerosis. Eur J Neurosci 20(10):2822-6. [PubMed: 15548226] [MGI Ref ID J:101282]
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]
Bories C; Amendola J; Lamotte d'Incamps B; Durand J. 2007. Early electrophysiological abnormalities in lumbar motoneurons in a transgenic mouse model of amyotrophic lateral sclerosis. Eur J Neurosci 25(2):451-9. [PubMed: 17284186] [MGI Ref ID J:118629]
Bruijn LI; Houseweart MK; Kato S; Anderson KL; Anderson SD; Ohama E; Reaume AG; Scott RW; Cleveland DW. 1998. Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1. Science 281(5384):1851-4. [PubMed: 9743498] [MGI Ref ID J:50039]
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]
Damiano M; Starkov AA; Petri S; Kipiani K; Kiaei M; Mattiazzi M; Flint Beal M; Manfredi G. 2006. Neural mitochondrial Ca capacity impairment precedes the onset of motor symptoms in G93A Cu/Zn-superoxide dismutase mutant mice. J Neurochem 96(5):1349-61. [PubMed: 16478527] [MGI Ref ID J:106152]
Kikuchi H; Almer G; Yamashita S; Guegan C; Nagai M; Xu Z; Sosunov AA; McKhann GM 2nd; Przedborski S. 2006. Spinal cord endoplasmic reticulum stress associated with a microsomal accumulation of mutant superoxide dismutase-1 in an ALS model. Proc Natl Acad Sci U S A 103(15):6025-30. [PubMed: 16595634] [MGI Ref ID J:108290]
Liu J; Shinobu LA; Ward CM; Young D; Cleveland DW. 2005. Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis. J Neurochem 93(4):875-82. [PubMed: 15857390] [MGI Ref ID J:98232]
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]
Rakhit R; Robertson J; Vande Velde C; Horne P; Ruth DM; Griffin J; Cleveland DW; Cashman NR; Chakrabartty A. 2007. An immunological epitope selective for pathological monomer-misfolded SOD1 in ALS. Nat Med 13(6):754-9. [PubMed: 17486090] [MGI Ref ID J:133800]
Raoul C; Buhler E; Sadeghi C; Jacquier A; Aebischer P; Pettmann B; Henderson CE; Haase G. 2006. Chronic activation in presymptomatic amyotrophic lateral sclerosis (ALS) mice of a feedback loop involving Fas, Daxx, and FasL. Proc Natl Acad Sci U S A 103(15):6007-12. [PubMed: 16581901] [MGI Ref ID J:108289]
Tummala H; Jung C; Tiwari A; Higgins CM; Hayward LJ; Xu Z. 2005. Inhibition of chaperone activity is a shared property of several Cu,Zn-superoxide dismutase mutants that cause amyotrophic lateral sclerosis. J Biol Chem 280(18):17725-31. [PubMed: 15753080] [MGI Ref ID J:99092]
Vijayvergiya C; Beal MF; Buck J; Manfredi G. 2005. Mutant superoxide dismutase 1 forms aggregates in the brain mitochondrial matrix of amyotrophic lateral sclerosis mice. J Neurosci 25(10):2463-70. [PubMed: 15758154] [MGI Ref ID J:134416]
Watanabe M; Dykes-Hoberg M; Culotta VC; Price DL; Wong PC; Rothstein JD. 2001. Histological evidence of protein aggregation in mutant SOD1 transgenic mice and in amyotrophic lateral sclerosis neural tissues. Neurobiol Dis 8(6):933-41. [PubMed: 11741389] [MGI Ref ID J:119899]
Watanabe S; Nagano S; Duce J; Kiaei M; Li QX; Tucker SM; Tiwari A; Brown RH Jr; Beal MF; Hayward LJ; Culotta VC; Yoshihara S; Sakoda S; Bush AI. 2007. Increased affinity for copper mediated by cysteine 111 in forms of mutant superoxide dismutase 1 linked to amyotrophic lateral sclerosis. Free Radic Biol Med 42(10):1534-42. [PubMed: 17448900] [MGI Ref ID J:121596]
Williamson TL; Bruijn LI; Zhu Q; Anderson KL; Anderson SD; Julien JP; Cleveland DW. 1998. Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant. Proc Natl Acad Sci U S A 95(16):9631-6. [PubMed: 9689132] [MGI Ref ID J:76716]
Williamson TL; Cleveland DW. 1999. Slowing of axonal transport is a very early event in the toxicity of ALS-linked SOD1 mutants to motor neurons. Nat Neurosci 2(1):50-6. [PubMed: 10195180] [MGI Ref ID J:55584]
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
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
This strain is currently Under Development for Distribution Colony.
To register your interest in this strain go to the Strain Interest Form.
Estimated Available for Sale Date: 08-DEC-08
Please note: Estimated available for sale dates are provided to keep customers better informed on strains under development. Please note that our Colony Managers routinely monitor the target date and edit it based on breeding performance and other factors. The length of time it takes to make a new strain available for sale depends on genotype, age, number of animals sent by the Donating Investigator, breeding performance, additional strain development (backcrossing, making homozygous), and anticipated demand for the strain/interest registered.
View All Strains Under Development and On Hold
Supply Details
| Standard Supply | Under Development for Distribution Colony |
|---|---|
| Supply Notes |
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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. | ||
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