JAX Mouse Strain Datasheet - 008248

B6.Cg-Tg(SOD1*G85R)148Dwc/J

Stock No:: 008248

Cryo Recovery

Overview

These G85R-SOD1 transgenic mice may be useful in studying neuromuscular disorders, including Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease).

Donating Investigator

Dr. Don Cleveland, Ludwig Institute for Cancer Research (UCSD)

Genetic overview

Genetic Background	Generation

Tg(SOD1*G85R)148Dwc

Allele Type
Transgenic (Humanized sequence, Inserted expressed sequence)

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Research Applications

Neurobiology Research

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed 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. Like wildtype SOD1, the G85R mutant SOD1 protein also forms monomer-misfolded oligomers associated with degenerating motor neurons.

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. On the C57BL/6 genetic background, hemizygous mice have a longer lifespan (median lifespan of 361 days). After the first initial phenotype observation, the disease progresses rapidly with death around 12-13 months of age. The onset and progression of motor dysfunction is accompanied by weight loss. For more detailed information, please view graph of B6.Cg-Tg(SOD1*G85R)148Dwc/J survival and weight data 2009-2010. [pdf]

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 these transgenic mice on a C57BL/6-congenic background may vary greatly 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.

Expression Data

Expressed Gene	SOD1, superoxide dismutase 1, human
Site of Expression

Control Suggestions

Noncarrier
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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.. In: . . MGI: J:77600

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Genetics

Tg(SOD1*G85R)148Dwc

Allele Symbol: Tg(SOD1*G85R)148Dwc

Allele Name	transgene insertion 148, Don W Cleveland
Allele Type	Transgenic (Humanized sequence, Inserted expressed sequence)
Allele Synonym(s)	148-G85R; G85R; G85R SOD1 line148; G85R line 148; SOD1 G85R line 148; Tg(SOD1-G85R)148Dwc
Gene Symbol and Name	Tg(SOD1*G85R)148Dwc, transgene insertion 148, Don W Cleveland
Gene Synonym(s)	148-G85R; G85R; G85R SOD1 line148; G85R line 148; SOD1 G85R line 148; Tg(SOD1-G85R)148Dwc; Tg(SOD1-G85R)148Dwc
Promoter	SOD1, superoxide dismutase 1, human
Expressed Gene	SOD1, superoxide dismutase 1, human
Strain of Origin	Not Applicable
Chromosome	UN
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.
Mutations Made By	Dr. Don Cleveland, Ludwig Institute for Cancer Research (UCSD)

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Amyotrophic Lateral Sclerosis (ALS)
- Neurodegeneration

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Tg(SOD1*G85R)148Dwc/?
Not Specified

nervous system phenotype

abnormal astrocyte morphology
- at 6 months of age round Lewy body-like inclusions are visible in astrocytes
- core consists of heterogeneous mass of short filamentous material covered with small granules
- inclusions have a dense core and a clear peripheral halo
- number of inclusions increases with age
- periphery has a less dense and, in some cases, linear array of filaments

abnormal motor neuron morphology
- aggregates progress to rounded Lewy body-like or irregular inclusions in cell bodies
- end-stage transgenics exhibit large inclusions in a few neurons in cell bodies and axonal processes
- prior to onset of disease a small number of motor neurons exhibit a few diffuse aggregates that are immunoreactive for SOD1 and ubiquitin

abnormal neuron morphology
- abnormalities are evident in ventral motor neurons, small neurons of the central canal and interneurons of the dorsal horns, however, no abnormalities are observed in cortical or subcortical structures

astrocytosis

axon degeneration
- among large axons, 7.5% of dorsal root axons are absent at end stage
- at 6.5 months a small number of large ventral motor neuron axons exhibit degeneration, although the loss is not significant
- at 8 months (disease onset) 25% of large motor axons are absent , of the remaining axons, 10% are undergoing degeneration and within another two weeks 66% are absent small caliber axons are not affected
- at 8 months 2.5% of large sensory axons are absent

decreased motor neuron number
- loss of motor neurons in ventral horn of spinal cord

behavior/neurological phenotype

decreased grip strength
- weakened grip strength, the first indication of phenotype, is observed by 8 months and spreads rapidly to other limbs

hindlimb paralysis
- hindlimb paralysis is first observed at 8-10 months
- paralysis occurs 2-3 days after appearance of hindlimb weakness

paralysis
- complete paralysis occurs two weeks after onset of weakened grip strength

muscle phenotype

muscular atrophy

progressive muscle weakness

References

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.. In: . . MGI: J:77600

Additional - Tg(SOD1*G85R)148Dwc related

Amendola J; Verrier B; Roubertoux P; Durand J. 2004. Altered sensorimotor development in a transgenic mouse model of amyotrophic lateral sclerosis.. In: . . MGI: J:101282
Bernard-Marissal N; Moumen A; Sunyach C; Pellegrino C; Dudley K; Henderson CE; Raoul C; Pettmann B. 2012. Reduced calreticulin levels link endoplasmic reticulum stress and Fas-triggered cell death in motoneurons vulnerable to ALS.. In: . . MGI: J:184132
Bidhendi EE; Bergh J; Zetterstrom P; Andersen PM; Marklund SL; Brannstrom T. 2016. Two superoxide dismutase prion strains transmit amyotrophic lateral sclerosis-like disease.. In: . . MGI: J:237077
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.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: J:50039
Carrasco DI; Bahr BA; Seburn KL; Pinter MJ. 2016. Abnormal response of distal Schwann cells to denervation in a mouse model of motor neuron disease.. In: . . MGI: J:229537
Carrasco DI; Seburn KL; Pinter MJ. 2016. Altered terminal Schwann cell morphology precedes denervation in SOD1 mice.. In: . . MGI: J:229558
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.. In: . . MGI: 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.. In: . . MGI: J:106152
Duplan L; Bernard N; Casseron W; Dudley K; Thouvenot E; Honnorat J; Rogemond V; De Bovis B; Aebischer P; Marin P; Raoul C; Henderson CE; Pettmann B. 2010. Collapsin response mediator protein 4a (CRMP4a) is upregulated in motoneurons of mutant SOD1 mice and can trigger motoneuron axonal degeneration and cell death.. In: . . MGI: J:157705
Filipchuk AA; Durand J. 2012. Postnatal dendritic development in lumbar motoneurons in mutant superoxide dismutase 1 mouse model of amyotrophic lateral sclerosis.. In: . . MGI: J:184723
Graffmo KS; Forsberg K; Bergh J; Birve A; Zetterstrom P; Andersen PM; Marklund SL; Brannstrom T. 2013. Expression of wild-type human superoxide dismutase-1 in mice causes amyotrophic lateral sclerosis.. In: . . MGI: J:191143
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.. In: . . MGI: J:108290
Leyton-Jaimes MF; Benaim C; Abu-Hamad S; Kahn J; Guetta A; Bucala R; Israelson A. 2016. Endogenous macrophage migration inhibitory factor reduces the accumulation and toxicity of misfolded SOD1 in a mouse model of ALS.. In: . . MGI: J:235587
Liebl MP; Kaya AM; Tenzer S; Mittenzwei R; Koziollek-Drechsler I; Schild H; Moosmann B; Behl C; Clement AM. 2014. Dimerization of visinin-like protein 1 is regulated by oxidative stress and calcium and is a pathological hallmark of amyotrophic lateral sclerosis.. In: . . MGI: J:212114
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.. In: . . MGI: 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.. In: . . MGI: J:133802
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.. In: . . MGI: J:146766
Marinkovic P; Reuter MS; Brill MS; Godinho L; Kerschensteiner M; Misgeld T. 2012. Axonal transport deficits and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis.. In: . . MGI: J:182236
Nguyen KT; Barrett JN; Garcia-Chacon L; David G; Barrett EF. 2011. Repetitive nerve stimulation transiently opens the mitochondrial permeability transition pore in motor nerve terminals of symptomatic mutant SOD1 mice.. In: . . MGI: J:172765
Nguyen KT; Zhang Z; Barrett EF; David G. 2012. Morphological and functional changes in innervation of a fast forelimb muscle in SOD1-G85R mice.. In: . . MGI: J:197508
Pehar M; Beeson G; Beeson CC; Johnson JA; Vargas MR. 2014. Mitochondria-targeted catalase reverts the neurotoxicity of hSOD1G(9)(3)A astrocytes without extending the survival of ALS-linked mutant hSOD1 mice.. In: . . MGI: J:219010
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.. In: . . MGI: 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.. In: . . MGI: J:108289
Robertson J; Sanelli T; Xiao S; Yang W; Horne P; Hammond R; Pioro EP; Strong MJ. 2007. Lack of TDP-43 abnormalities in mutant SOD1 transgenic mice shows disparity with ALS.. In: . . MGI: J:143016
Tokuda E; Okawa E; Watanabe S; Ono S; Marklund SL. 2013. Dysregulation of intracellular copper homeostasis is common to transgenic mice expressing human mutant superoxide dismutase-1s regardless of their copper-binding abilities.. In: . . MGI: J:197756
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.. In: . . MGI: J:99092
Vargas MR; Burton NC; Kutzke J; Gan L; Johnson DA; Schafer M; Werner S; Johnson JA. 2013. Absence of Nrf2 or its selective overexpression in neurons and muscle does not affect survival in ALS-linked mutant hSOD1 mouse models.. In: . . MGI: J:199339
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.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: 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.. In: . . MGI: J:55584
Zhai J; Zhou W; Li J; Hayworth CR; Zhang L; Misawa H; Klein R; Scherer SS; Balice-Gordon RJ; Kalb RG. 2011. The in vivo contribution of motor neuron TrkB receptors to mutant SOD1 motor neuron disease.. In: . . MGI: J:176684
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.. In: . . MGI: J:136100

Service	Genotype	Price
	Hemizygous or Non carrier for Tg(SOD1*G85R)148Dwc

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(SOD1*G85R)148Dwc

Allele Symbol: Tg(SOD1*G85R)148Dwc

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(SOD1*G85R)148Dwc/?Not Specified

nervous system phenotype

behavior/neurological phenotype

muscle phenotype

References

Additional - Tg(SOD1*G85R)148Dwc related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Not-For-Profit & Academic Pricing

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Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(SOD1*G85R)148Dwc/?
Not Specified