MnSODtet functions as a knockout allele (abolishes MnSOD expression) in the absence of doxycycline. MnSODtet mice may be useful for studying the role of antioxidants in cellular metabolism and aging, and in mitochondria function.
Joel S Greenberger, University of Pittsburgh
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Inducible, Null/Knockout, Inserted expressed sequence) | Sod2 | superoxide dismutase 2, mitochondrial |
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.
MnSODtet functions as a knockout allele (abolishes MnSOD expression) in the absence of doxycycline (dox). Both male and female heterozygous (MnSODtet/+) mice are viable and fertile with normal phenotype, regardless of doxycycline treatment. The donating investigator reports that in the absence of dox, homozygous (MnSODtet/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.
The MnSODtet-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 (neor), polyA sequence, loxP site and five copies of tetracycline operator 5prime of a minimal cytomegalovirus promoter (tetO+CMV [or teto5 CMV]). The Tet-On regulatory fragment is a modification of the neor 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 MnSODtet-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 MnSODtet 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 MnSODtet mouse colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6NJ inbred females (Stock No. 005304).
Expressed Gene | rtTA, reverse tetracycline-controlled transactivator, E. coli |
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Site of Expression | Administration of doxycycline controls expression of Sod2 in mitochondria. |
Allele Name | targeted mutation 1, Joel Greenberger |
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Allele Type | Targeted (Inducible, Null/Knockout, Inserted expressed sequence) |
Allele Synonym(s) | MnSODtet |
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 |
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.
When using the MnSODtet mouse strain in a publication, please cite the originating article(s) and include JAX stock #024851 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Sod2<tm1(rtTA*M2,tetO)Jsg> |
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 |
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