Overview

Also Known As:SOD2^m1BCM

Mice homozygous for this targeted mutation of mouse Sod2 (superoxide dismutase 2, mitochondrial) are embryonic lethal. Crosses with DBA/2J inbred mice enhance homozygous viability and produce animals exhibiting severe wasting and progressive ataxia.

Donating Investigator

Dr. Russell Lebovitz, SUMA Partners

Genetic overview

Genetic Background	Generation

Sod2^tm1Leb

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Sod2	superoxide dismutase 2, mitochondrial

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Research Applications

Metabolism Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Original studies of this strain, first published in 1996, describe homozygous animals that died within 21 days of birth and exhibited several novel pathogenic phenotypes including severe anemia, degeneration of neurons in the basal ganglia and brainstem, progressive motor disturbances, and myocardial injury. Applications included studies of idiopathic cardiomyopathy and sporadic motor neuron disease.

It has been found, however, that mice homozygous for the Sod2^tm1Leb mutation on the current C57BL/6 genetic background (backcross generation N5+25 - July, 2017) are embryonic lethal. In one recent study, heterozygote x heterozygote crosses produced no homozygous mutants at P0-P1 (0/40 pups; unpublished).

Improved homozygous viability has been demonstrated in matings of B6.129S7-Sod2^tm1Leb/J (Stock# 002973) mutant mice with DBA/2J inbred animals (Stock# 000671). Intercrosses of F1 animals yield F2 homozygous pups at a lower-than-predicted Mendelian percentage, but they have a median survival time of 12 days. The C57BL/6-DBA/2J (B6D2F2) mixed background mutant animals (not currently offered by The Jackson Laboratory) display severe wasting and progressive ataxia. The heart and brain have not been examined histologically. This data has not been published (July, 2017).

Development

The Sod2^tm1Leb targeted mutation was made by Dr. Russell Lebovitz. A 1.5 Kb HindIII fragment containing exons 1 and 2 of the Sod2 gene, as well as approximately 500bp immediately 5' of exon 1, was replaced with a human hypoxanthine phosphoribosyltransferase minigene driven by the phosphoglycerate kinase promoter. The transcription and translation start sites, the mitochondrial targeting sequence, and one of the three histidines that bind directly to the manganese cofactor, have been eliminated. The 129S7/SvEvBrd-Hprt^b-m2-derived AB 2.1 ES cell line was used. The Sod2^tm1Leb targeted mutation was initially backcrossed more than 5 times to C57BL/6 mice prior to arrival at The Jackson Laboratory. A further 25 generations of backcrossing to C57BL/6J have subsequently occurred (July, 2017).

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Lebovitz RM; Zhang H; Vogel H; Cartwright J Jr; Dionne L; Lu N; Huang S; Matzuk MM. 1996. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci U S A 93(18):9782-7PubMed: 8790408 MGI: J:36148

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Genetics

Sod2^tm1Leb

Allele Symbol: Sod2^tm1Leb

Allele Name	targeted mutation 1, Russell M Lebovitz
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Sod2^-; SOD2^m1BCM; Sod2^mlbcm
Gene Symbol and Name	Sod2, superoxide dismutase 2, mitochondrial
Gene Synonym(s)
Strain of Origin	129S7/SvEvBrd-Hprt^b-m2
Chromosome	17
Molecular Note	A human HPRT minigene driven by the PGK promoter replaced exons 1 and 2, and sequences approximately 500 bp immediately 5' of exon 1. The replaced region encodes the transcription and translation start sites, the mitochondrial targeting sequence, and one of three histidines that bind directly to the manganese cofactor. Northern blot analysis of brain did not detect mRNA in homozygous mutant mice. Enzyme activity assays of heart did not detect active protein in homozygous mutant mice.
Mutations Made By	Dr. Russell Lebovitz, SUMA Partners

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Genotype: Sod2^tm1Leb related

Metabolism Research
Neurobiology Research
- Metabolic Defects
- Neurodegeneration

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Sod2^tm1Leb/Sod2^tm1Leb
B6.129S7-Sod2/J

adipose tissue phenotype

decreased total body fat amount
- homozygotes display a significant reduction in adipose tissue mass

growth/size/body region phenotype

postnatal growth retardation
- reduction of postnatal growth rate is variable among mice, first evident between P2 and P7, and progressive until death by P18

decreased body length

decreased body size
- at P10, homozygotes are significantly smaller than wild-type littermates
- Normal - however, no skeletal abnormalities are observed and failure to thrive is unrelated to nursing difficulties

decreased body weight

hematopoietic system phenotype

decreased bone marrow cell number
- homozygotes display a hypocellular bone marrow

impaired myelopoiesis
- within the bone marrow, all hematopoietic lineages appear to be reduced

anemia
- homozygotes are severely anemic at the time of death

homeostasis/metabolism phenotype

abnormal lipid homeostasis
- homozygotes with extreme cardiac dilatation exhibit lipid peroxidation of mitochondrial membranes in affected myocytes
- homozygotes display an abundance of intracellular lipid vacuoles in hepatocytes
- homozygotes without extreme cardiac dilatation show increased accumulation of neutral lipid in myocytes but no mitochondrial injury

behavior/neurological phenotype

abnormal motor capabilities/coordination/movement
- homozygotes display striking and progressive motor deficits

circling

weakness
- homozygotes exhibit progressive limb weakness, as shown by impaired ability to hold onto a bar suspended above the cage for at least 5 sec without falling or scale a 60 degree incline

fatigue
- homozygotes display earlier onset of fatigue, as shown by reduced endurance only after 2-3 cycles of immersion into a small room-temperature water bath (vs 10 cycles in wild-type mice)

immune system phenotype

impaired myelopoiesis
- within the bone marrow, all hematopoietic lineages appear to be reduced

integument phenotype

pallor
- homozygotes appear slightly pale

liver/biliary system phenotype

abnormal hepatocyte morphology
- in addition, an abundance of intracellular lipid vacuoles is observed
- hepatic glycogen deposits appear coarsely granular and with a tendency towards centrilobular accumulation

mammalian phenotype

reproductive system phenotype
- Normal - ovaries from female homozygotes (4-10 days of age), transplanted to the bursa of wild-type hosts, display all stages of folliculogenesis including corpora lutea and give rise to viable offspring, suggesting normal ovarian function

mortality/aging

postnatal lethality, complete penetrance
- mutants with intermediate growth rates die within the second or third week
- homozygotes survive for up to 3 weeks of age
- mutants with the slowest growth rates (4 of 8) usually die during the first postnatal week

muscle phenotype

decreased skeletal muscle mass
- homozygotes display a significant reduction in skeletal muscle mass

dilated cardiomyopathy
- affected myocytes exhibit widespread cellular injury and death associated with mitochondrial injury (swelling and fragmentation) and lipid peroxidation of mitochondrial membranes in severely affected resgions
- only 10% of homozygotes display extreme baloon-like cardiac dilatation with thinning of the ventricular wall

nervous system phenotype

neurodegeneration
- neurodegeneration is associated with extensive mitochondrial damage, loss of polysomes, clearing of the cytoplasm, a relative absence of rough ER, focal dilation of smooth ER, and ruffling of nuclear membranes
- homozygotes display degeneration of large CNS neurons, esp. in the basal ganglia and brainstem
- in P10 basal ganglia, early cellular degeneration includes dispersion of cytoplasm, shedding of ribosomes, and balloning of mitochondria
- in affected brain and brainstem regions, occasional swollen neurites are observed; however, most structures and mitochondria remain intact

cardiovascular system phenotype

thin ventricular wall
- homozygotes with extreme baloon-like cardiac dilatation (10%) display thinning of the ventricular wall

dilated cardiomyopathy
- only 10% of homozygotes display extreme baloon-like cardiac dilatation with thinning of the ventricular wall
- affected myocytes exhibit widespread cellular injury and death associated with mitochondrial injury (swelling and fragmentation) and lipid peroxidation of mitochondrial membranes in severely affected resgions

cellular phenotype

abnormal mitochondrial physiology
- at >P7, homozygotes show extensive mitochondrial injury in affected cardiac muscle cells and degenerating neurons

Genotype: Sod2^tm1Leb/Sod2⁺
B6.129S7-Sod2/J

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - aging heterozygotes exhibit no significant increase in the amount of age-related hearing loss relative to C57BL/6 control mice, with many animals over the age of 20 months being deaf or displaying ABR thresholds >80 dB SPL
- Normal - vely good hearing of three 24-month-old heterozygotes is provided
- Normal - contrary to expectation, ABR thresholds are only 12 dB higher in heterozygotes relative to C57BL/6 control mice (at various age groups including 6-9, 12, 15, 18-21 and 24 months and stimuli including click, 8, 16 and 32 kHz); no explanation for the relatively good hearing of three 24-month-old heterozygotes is provided

References

Lebovitz RM; Zhang H; Vogel H; Cartwright J Jr; Dionne L; Lu N; Huang S; Matzuk MM. 1996. Neurodegeneration, myocardial injury, and perinatal death in mitochondrial superoxide dismutase-deficient mice. Proc Natl Acad Sci U S A 93(18):9782-7PubMed: 8790408 MGI: J:36148

Additional - Sod2^tm1Leb related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Human HPRT
- Standard PCR:Sod2
- Genotyping resources and troubleshooting
Breeding Considerations

This strain is maintained by mating heterozygotes (female or male) with C57BL/6J inbred mice. Homozygotes are embryonic lethal.
- Additional Breeding and Husbandry Support
Appearance
- black
  Related Genotype: a/a
Citation
When using the SOD2^m1BCM mouse strain in a publication, please cite the originating article(s) and include JAX stock #002973 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 Wild-type for Sod2<tm1Leb>

Payment Terms and Conditions

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.

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

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:SOD2m1BCM

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Sod2tm1Leb

Allele Symbol: Sod2tm1Leb

Disease Terms

Research Areas By Phenotype

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

Genotype: Sod2tm1Leb related

Mammalian Phenotype Terms by Genotype

Genotype: Sod2tm1Leb/Sod2tm1LebB6.129S7-Sod2/J

adipose tissue phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

behavior/neurological phenotype

immune system phenotype

integument phenotype

liver/biliary system phenotype

mammalian phenotype

mortality/aging

muscle phenotype

nervous system phenotype

cardiovascular system phenotype

cellular phenotype

Genotype: Sod2tm1Leb/Sod2+B6.129S7-Sod2/J

mammalian phenotype

References

Additional - Sod2tm1Leb related

Genotyping Protocols

Breeding Considerations

Appearance

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

Licensing Information

Also Known As:SOD2^m1BCM

Sod2^tm1Leb

Allele Symbol: Sod2^tm1Leb

Genotype: Sod2^tm1Leb related

Genotype: Sod2^tm1Leb/Sod2^tm1Leb
B6.129S7-Sod2/J

Genotype: Sod2^tm1Leb/Sod2⁺
B6.129S7-Sod2/J

Additional - Sod2^tm1Leb related