Overview

Also Known As:MnSOD^tet

MnSOD^tet functions as a knockout allele (abolishes MnSOD expression) in the absence of doxycycline. MnSOD^tet mice may be useful for studying the role of antioxidants in cellular metabolism and aging, and in mitochondria function.

Donating Investigator

Joel S Greenberger, University of Pittsburgh

Genetic overview

Genetic Background	Generation

Sod2^{tm1(rtTAM2,tetO)Jsg}*

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

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Research Applications

Research Tools
Cell Biology Research
Neurobiology Research
Metabolism Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

MnSOD (Sod2) is a major antioxidant for the conversion of superoxide produced in the mitochondria during respiration. It has also been shown to be important in protecting the mtiochondria and the cell from irradiation damage. These mice may be useful for studying the role of antioxidants in cellular metabolism aging and in the functioning of the mitochondria.

MnSOD^tet functions as a knockout allele (abolishes MnSOD expression) in the absence of doxycycline (dox). Both male and female heterozygous (MnSOD^tet/+) mice are viable and fertile with normal phenotype, regardless of doxycycline treatment. The donating investigator reports that in the absence of dox, homozygous (MnSOD^tet/tet) newborn mice die within seven days of birth, similar to MnSOD knockout mice. Homozygous mice are smaller than heterozygous or wildtype littermates until weaning, and are similar sized thereafter. At around 5 to 6 weeks of age, homozygotes can be taken off dox and are able to maintain body weight and health for at least one month. The donating investigator also reports that when breeding heterozygotes together, 1 of 10 homozygous pups given dox will survive to weaning. Administration of dox water to nursing dams does not lead to increased survival of homozygous pups; the most effective way to keep homozygous pups alive is by dox injection. Homozygous mice on dox are fertile but have fewer litters.

Development

The MnSOD^tet-on targeting vector was designed by Drs. J. Richard Chaillet, Joel S. Greenberger and Michael W. Epperly (University of Pittsburgh School of Medicine) to insert a 5.3 kbp Tet-On regulatory cassette approximately 30 nucleotides upstream of the initiation codon in the first exon of the manganese superoxide dismutase (Sod2 or MnSOD) gene on chromosome 17. The Tet-On regulatory cassette contains the optimized form of reverse tetracycline controlled transactivator (rtTA-M2), polyA sequence, loxP site, neomycin resistance gene (neo^r), polyA sequence, loxP site and five copies of tetracycline operator 5prime of a minimal cytomegalovirus promoter (tetO+CMV [or tet_o5 CMV]). The Tet-On regulatory fragment is a modification of the neo^r version of Tet-Off regulatory cassette. The Tet-Off cassette was converted to Tet-On by changing five codons via site-directed mutagenesis: S12G(GGC), E19G(GGG), A56P(CCC), D148E(GAG) and H179R(CGC). These amino acid changes converted tTA to the M2 form of rtTA (rtTA-M2). The MnSOD^tet-on construct was electroporated into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Chimeric animals were bred with C57BL/6NTac mice to establish the colony. The MnSOD^tet colony was backcrossed onto the C57BL/6NTac genetic background for six generations. In 2014, black heterozygous males were sent to The Jackson Laboratory Repository. Upon arrival, males were used to cryopreserve sperm. To establish our living MnSOD^tet mouse colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6NJ inbred females (Stock No. 005304).

Expression Data

Expressed Gene	rtTA, reverse tetracycline-controlled transactivator, E. coli
Site of Expression	Administration of doxycycline controls expression of Sod2 in mitochondria.

Control Suggestions

Wild-type from the colony

Approximate Controls

005304 C57BL/6NJ

Additional Information

Considerations for Choosing Controls

Selected References

Epperly MW; Chaillet JR; Kalash R; Shaffer B; Goff J; Franicola D; Zhang X; Dixon T; Houghton F; Wang H; Berhane H; Romero C; Kim JH; Greenberger JS. 2013. Conditional radioresistance of Tet-inducible manganese superoxide dismutase bone marrow stromal cell lines. Radiat Res 180(2):189-204PubMed: 23862693 MGI: J:209713

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Genetics

Sod2^{tm1(rtTAM2,tetO)Jsg}*

Allele Symbol: Sod2^{tm1(rtTAM2,tetO)Jsg}*

Allele Name	targeted mutation 1, Joel Greenberger
Allele Type	Targeted (Inducible, Null/Knockout, Inserted expressed sequence)
Allele Synonym(s)	MnSOD^tet
Gene Symbol and Name	Sod2, superoxide dismutase 2, mitochondrial
Gene Synonym(s)
Promoter	tetO, tet operator,
Expressed Gene	rtTA, reverse tetracycline-controlled transactivator, E. coli
Site of Expression	Administration of doxycycline controls expression of Sod2 in mitochondria.
Strain of Origin	129S6/SvEvTac
Chromosome	17
Molecular Note	The MnSOD targeting vector was designed to insert a 5.3 kbp Tet-On regulatory cassette approximately 30 nucleotides upstream of the initiation codon in the first exon. The Tet-On regulatory cassette contains the optimized form of reverse tetracycline controlled transactivator (rtTA-M2), polyA sequence, loxP site, neomycin resistance gene (neo), polyA sequence, loxP site and five copies of tetracycline operator 5' of a minimal cytomegalovirus promoter. The Tet-On regulatory fragment is a modification of the neo version of Tet-Off regulatory cassette. The Tet-Off cassette was converted to Tet-On by changing five codons via site-directed mutagenesis: S12G(GGC), E19G(GGG), A56P(CCC), D148E(GAG) and H179R(CGC). These amino acid changes converted tTA to the M2 form of rtTA (rtTA-M2).

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Research Tools
- Tet Expression Systems
  - tTA/rtTA Expressing Strains
  - tTA/rtTA Responsive Strains
- Cancer Research
  - Tetop Tet System
- Cardiovascular Research
  - Tetop Tet System
- Genetics Research
  - Mutagenesis and Transgenesis: Tetop Tet System
- Neurobiology Research
  - Tetop Tet System
- Reproductive Biology Research
  - Tetop Tet System
- Cell Biology Research
- Toxicology Research
  - free radical research
- Metabolism Research
Cell Biology Research
- Genes Regulating Growth and Proliferation
Neurobiology Research
- Tet Expression System
  - tTA/rtTA Responsive Strains
  - tTA/rtTA Expressing Strains
- Metabolic Defects
Metabolism Research
- Free Radical Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Sod2^{tm1(rtTAM2,tetO)Jsg}/Sod2^{tm1(rtTAM2,tetO)Jsg}
involves: 129S6/SvEvTac * C57BL/6

cellular phenotype

increased cell death
- bone marrow stromal cell lines generated from homozygous mice exhibit decreased viability 7 days after irradiation as compared to control cells
- total number of cells is decreased 14 days after irradiation as compared to control cells

increased cellular sensitivity to gamma-irradiation
- irradiated bone marrow stromal cell lines generated from homozygous mice exhibit increased radiosensitivity as compared to control cells

abnormal double-strand DNA break repair
- irradiated bone marrow stromal cell lines generated from homozygous mice exhibit impaired double stranded break repair as compared to control cells

abnormal redox activity
- antioxidant stores are significantly increased in irradiated bone marrow stromal cell lines incubated with doxycycline as compared to irradiated wild-type cell lines

homeostasis/metabolism phenotype

abnormal double-strand DNA break repair
- irradiated bone marrow stromal cell lines generated from homozygous mice exhibit impaired double stranded break repair as compared to control cells

References

Epperly MW; Chaillet JR; Kalash R; Shaffer B; Goff J; Franicola D; Zhang X; Dixon T; Houghton F; Wang H; Berhane H; Romero C; Kim JH; Greenberger JS. 2013. Conditional radioresistance of Tet-inducible manganese superoxide dismutase bone marrow stromal cell lines. Radiat Res 180(2):189-204PubMed: 23862693 MGI: J:209713

Additional - Sod2^{tm1(rtTAM2,tetO)Jsg}* related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Generic rtTA-Alternate 1
- Standard PCR:Sod2alternate2
- Probe:Generic rtTA-Alternate 1
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6NJ inbred mice (Stock No. 005304). The donating investigator reports that when breeding heterozygotes together, 1 of 10 homozygous pups given dox will survive to weaning. Administration of dox water to nursing dams does not lead to increased survival of homozygous pups; the most effective way to keep homozygous pups alive is by dox injection. Homozygous mice on dox are fertile but have fewer litters.
- Additional Breeding and Husbandry Support
Citation
When using the MnSOD^tet mouse strain in a publication, please cite the originating article(s) and include JAX stock #024851 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 Sod2<tm1(rtTA*M2,tetO)Jsg>

Related Products and Services

Frozen Mouse Embryo	B6N.129S6-Sod2<tm1(rtTA*M2 tetO)Jsg>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6N.129S6-Sod2<tm1(rtTA*M2 tetO)Jsg>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6N.129S6-Sod2<tm1(rtTA*M2 tetO)Jsg>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6N.129S6-Sod2<tm1(rtTA*M2 tetO)Jsg>/J Frozen Embryo	$3373.50

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

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:MnSODtet

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Sod2tm1(rtTA*M2,tetO)Jsg

Allele Symbol: Sod2tm1(rtTA*M2,tetO)Jsg

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Sod2tm1(rtTA*M2,tetO)Jsg/Sod2tm1(rtTA*M2,tetO)Jsginvolves: 129S6/SvEvTac * C57BL/6

cellular phenotype

homeostasis/metabolism phenotype

References

Additional - Sod2tm1(rtTA*M2,tetO)Jsg 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

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Also Known As:MnSOD^tet

Sod2^{tm1(rtTAM2,tetO)Jsg}*

Allele Symbol: Sod2^{tm1(rtTAM2,tetO)Jsg}*

Genotype: Sod2^{tm1(rtTAM2,tetO)Jsg}/Sod2^{tm1(rtTAM2,tetO)Jsg}
involves: 129S6/SvEvTac * C57BL/6

Additional - Sod2^{tm1(rtTAM2,tetO)Jsg}* related