Overview

Sod1^D83G ENU-induced mutant mice possess a missense mutation in exon 3 of the Sod1 gene. These mutant mice may be useful in studying the effects of SOD1 protein regulation on the development of amyotrophic lateral sclerosis and motor neuron disease. They are a useful tool for separating the effects of central neuronal death from the peripheral distal neuropathy.

Donating Investigator

Elizabeth MC Fisher, UCL Institute of Neurology

Genetic overview

Genetic Background	Generation

Sod1^m1H

Allele Type	Gene Symbol	Gene Name
Chemically induced (ENU)	Sod1	superoxide dismutase 1, soluble

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Research Applications

Neurobiology Research
Developmental Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These Sod1^D83G ENU-induced mutant mice possess a missense mutation in exon 3 of the superoxide dismutase 1 (Sod1) gene. SOD1 is a widely expressed isozyme responsible for destroying free superoxide radicals. SOD1 mutations, including SOD1*D83G, are known to cause Lou Gehrig's disease (Amyotrophic lateral sclerosis; ALS)/motor neuron disease (MND). These mutant mice produce the same mRNA levels as wildtype mice but contain decreased amounts of mutant SOD1 protein, leading to a dose dependant decrease in dismuatase activity. Homozygotes mice are not produced in a Mendelian ratio. They develop a degeneration of the lower and upper motor neurons between 6 and 15 weeks of age. This neuronal cell death ceases in adulthood and the mice do not become paralyzed. However, motor ability continues to deteriorate after 15 weeks of age in homozygous mutants. . This motor dysfunction is underlined by a progressive distal denervation of the neuromuscular junctions of the extensor digitorum longus hindlimb muscle between 15 and 52 weeks of age, leading to progressive peripheral neuropathy. These mice have a reduced life span, and they develop liver tumors, tremors, reduced pelvic elevation, significant sensory deficits. Heterozygotes are viable and fertile, and have a phenotype similar to wildtype littermates, except for in cage motor ability.

Development

Following multidose N-ethyl-N-nitrosourea (ENU) treatments to induce mutations in founder male C57BL/6J mice, a reverse genetic screen was utilized to identify mice with a mutation in the superoxide dismutase 1 (Sod1) gene. Males were bred with C3H/HeH females and sperm from F1 males was screened for mutations in Sod1. A mutation was mapped with Sanger sequencing and an A to G transition in exon 3 of Sod1 resulting in an aspartic acid to glycine missense mutation (D83G). Sperm from Sod1^D83G F1 males was used for in vitro fertilization of C57BL/6J oocytes. These Sod1^D83G mice were bred to C57BL/6J mice for at least 10 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Joyce PI; Mcgoldrick P; Saccon RA; Weber W; Fratta P; West SJ; Zhu N; Carter S; Phatak V; Stewart M; Simon M; Kumar S; Heise I; Bros-Facer V; Dick J; Corrochano S; Stanford MJ; Luong TV; Nolan PM; Meyer T; Brandner S; Bennett DL; Ozdinler PH; Greensmith L; Fisher EM; Acevedo-Arozena A. 2015. A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity. Hum Mol Genet 24(7):1883-97PubMed: 25468678 MGI: J:219360

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Genetics

Sod1^m1H

Allele Symbol: Sod1^m1H

Allele Name	mutation 1, Harwell
Allele Type	Chemically induced (ENU)
Allele Synonym(s)	Sod1^D83G
Gene Symbol and Name	Sod1, superoxide dismutase 1, soluble
Gene Synonym(s)
Strain of Origin	C57BL/6J
Chromosome	16
Molecular Note	ENU mutagenesis induced an A to G transition in exon 3 that results in an aspartic acid toglycine missense mutation (D83G). Dismutase activity of the mutant protein is severely reduced compared to the wild-type protein.

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

amyotrophic lateral sclerosis type 1

Research Areas By Phenotype

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

Neurobiology Research
- Neuromuscular defects
- Amyotrophic Lateral Sclerosis (ALS)
- Neurodegeneration
- Ataxia (Movement) Defects
- Behavioral and Learning Defects
Developmental Biology Research
- Neurodevelopmental Defects

Mammalian Phenotype Terms by Genotype

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

Genotype: Sod1^m1H/Sod1^m1H
involves: C3H/HeH * C57BL/6J

adipose tissue phenotype

abnormal body fat mass
- mice show less fat mass at 52 weeks of age

growth/size/body region phenotype

abnormal body fat mass
- mice show less fat mass at 52 weeks of age

decreased body weight
- reduction in body weight from 4 weeks of age

hematopoietic system phenotype

microgliosis
- microgliosis is seen in the lumbar spinal cord at 15 weeks of age and increases further at 52 weeks of age

immune system phenotype

liver inflammation
- liver at autopsy shows moderate parenchymal inflammation

microgliosis
- microgliosis is seen in the lumbar spinal cord at 15 weeks of age and increases further at 52 weeks of age

integument phenotype

hyporesponsive to tactile stimuli
- females exhibit a sensory deficit in response to a low threshold mechanical stimulus
- Normal - however, females do not show deficits toward a high-threshold mechanical stimulus

increased thermal nociceptive threshold
- females exhibit a sensory deficit in response noxious heat stimulus
- Normal - however, females do not show deficits toward a noxious cold stimulus (cold plate)

behavior/neurological phenotype

abnormal gait
- mice develop gait abnormalities with age

decreased grip strength
- mice exhibit reduced grip strength from 6 weeks of age

hyporesponsive to tactile stimuli
- females exhibit a sensory deficit in response to a low threshold mechanical stimulus
- Normal - however, females do not show deficits toward a high-threshold mechanical stimulus

impaired coordination
- mice show impaired performance on the accelerating rotarod, with females showing earlier deficits (23 weeks) than males (67 weeks)

increased thermal nociceptive threshold
- females exhibit a sensory deficit in response noxious heat stimulus
- Normal - however, females do not show deficits toward a noxious cold stimulus (cold plate)

positive geotaxis
- ability to walk down a vertical wire grate (negative geotaxis) is impaired

tremors
- mice develop tremors with age

liver/biliary system phenotype

abnormal liver morphology
- liver at autopsy shows diffuse nuclear anisocytosis, moderate parenchymal inflammation and patchy fatty change

increased hepatocellular carcinoma incidence

increased liver tumor incidence
- mice exhibit more liver tumors at autopsy than wild-type mice

liver inflammation
- liver at autopsy shows moderate parenchymal inflammation

mortality/aging

lethality, incomplete penetrance
- fewer than the expected numbers of homozygotes are obtained

premature death
- shorter survival, with males having a significantly reduced lifespan compared to females (495 days vs. 588 days, respectively)

muscle phenotype

abnormal muscle fiber morphology
- mice exhibit changes in the histochemical phenotype of fast twitch muscles indicative of an oxidative phenotype that is more characteristic of slow twitch, type I muscle fibers

progressive muscle weakness
- progressive loss in muscle strength between 15 and 52 weeks of age, with weaker tibialis anterior muscle at 15 weeks that declines further at 52 weeks, and a reduction in muscle force of EDL by about 35% in 52 week old females
- the fatigue index of EDL is normal at 15 weeks of age but is increased by 30% at 52 weeks of age

neoplasm

increased hepatocellular carcinoma incidence

increased liver tumor incidence
- mice exhibit more liver tumors at autopsy than wild-type mice

nervous system phenotype

abnormal corticospinal tract morphology
- mice show signs of cellular degeneration of corticospinal motor neurons in layer V of the motor cortex at 29 weeks of age

abnormal motor neuron innervation pattern
- mice exhibit an increase in denervated endplate neuromuscular junctions in the extensor digitorum longus (EDL) at 52, but not 15, weeks of age indicating distal progressive denervation of the EDL muscle

astrocytosis
- astrogliosis is seen in the lumbar spinal cord at 15 weeks of age and increases further at 52 weeks of age

decreased motor neuron number
- corticospinal motor neuron numbers are normal at 15 weeks of age but are reduced by 22% at 29 weeks of age

microgliosis
- microgliosis is seen in the lumbar spinal cord at 15 weeks of age and increases further at 52 weeks of age

motor neuron degeneration
- mice develop lower motor neuron 9in the lumbar spinal cord) degeneration between 6 and 15 weeks of age, showing a 23% reduction in the number of lower motor neurons at 15 weeks of age, which remains stable at 52 weeks of age
- mice develop upper motor neuron degeneration between 15 and 29 weeks of age, with a 22% reduction in corticospinal motor neuron numbers at 29 weeks

skeleton phenotype

kyphosis
- mice become severely kyphotic with age

Genotype: Sod1^m1H/Sod1⁺
involves: C3H/HeH * C57BL/6J

behavior/neurological phenotype

abnormal locomotor activation
- 88 week old mutants show a reduction in the duration for each running bout when compared to 44 week old mutants unlike wild-type mice that show an increase in the duration at 88 weeks compared to 44 weeks
- mice show a reduction in the duration per running bout at 44 and 88 weeks compared to wild-type mice

hypoactivity
- mice exhibit a deficit in nightly total distance traveled which declines with age

cellular phenotype

abnormal mitochondrial physiology
- in embryonic motor neurons, mitochondrial membrane potential is elevated compared to wild-type

nervous system phenotype

abnormal neuron physiology
- Normal - however, mice do not exhibit motor neuron loss up to 52 weeks of age
- in embryonic motor neurons, mitochondrial membrane potential is elevated compared to wild-type

References

Joyce PI; Mcgoldrick P; Saccon RA; Weber W; Fratta P; West SJ; Zhu N; Carter S; Phatak V; Stewart M; Simon M; Kumar S; Heise I; Bros-Facer V; Dick J; Corrochano S; Stanford MJ; Luong TV; Nolan PM; Meyer T; Brandner S; Bennett DL; Ozdinler PH; Greensmith L; Fisher EM; Acevedo-Arozena A. 2015. A novel SOD1-ALS mutation separates central and peripheral effects of mutant SOD1 toxicity. Hum Mol Genet 24(7):1883-97PubMed: 25468678 MGI: J:219360

Additional - Sod1^m1H related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Sanger sequencing:Sod1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664). Homozygous mice are not born at mendelian ratios, and develop peripheral neuropathy as adults.
- Additional Breeding and Husbandry Support
Citation
When using the B6(C3H)-Sod1^m1H/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #020440 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Sod1<m1H>

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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General Terms and Conditions

Questions about Terms of Use

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Licensing Information

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Email: TechTran@jax.org

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Sod1m1H

Allele Symbol: Sod1m1H

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Sod1m1H/Sod1m1Hinvolves: C3H/HeH * C57BL/6J

adipose tissue phenotype

growth/size/body region phenotype

hematopoietic system phenotype

immune system phenotype

integument phenotype

behavior/neurological phenotype

liver/biliary system phenotype

mortality/aging

muscle phenotype

neoplasm

nervous system phenotype

skeleton phenotype

Genotype: Sod1m1H/Sod1+involves: C3H/HeH * C57BL/6J

behavior/neurological phenotype

cellular phenotype

nervous system phenotype

References

Additional - Sod1m1H 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 - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

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

Sod1^m1H

Allele Symbol: Sod1^m1H

Genotype: Sod1^m1H/Sod1^m1H
involves: C3H/HeH * C57BL/6J

Genotype: Sod1^m1H/Sod1⁺
involves: C3H/HeH * C57BL/6J

Additional - Sod1^m1H related