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| C57BL/6.mCAT mice (MCAT transgenic mice) have a CMV enhancer/chicken beta-actin promoter driving the expression of human Catalase gene in mitochondria. These mice may be useful for studying the role of reactive oxygen species in mammalian longevity, as well as protection from lung adenocarcinoma. | |||||||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Former Names B6.Cg-Tg(CAG-OTC/CAT)4033Wcl/J (Changed: 05-APR-11 ) Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Noncarrier x Hemizygote (Female x Male) 22-SEP-11 Mating System Hemizygote x Noncarrier (Female x Male) 22-SEP-11 Species laboratory mouse Generation ?+F2 (07-JAN-13)
Generation DefinitionsDonating Investigator Peter S Rabinovitch, University of Washington Description
C57BL/6.mCAT mice (MCAT transgenic mice) have a CMV enhancer/chicken beta-actin promoter (CAG; from the pCAGGS vector) driving the expression of a human Catalase (CAT) gene in mitochondria. Hemizygous MCAT mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Catalase is a an enzyme, normally expressed in peroxisomes, that reduces hydrogen peroxide (H2O2) to water and molecular oxygen, mitigating the potential for H2O2 to cause damage to molecules. Mitochondrial catalase expression in MCAT mice results in a 5.5-month increase in median life span for both males and females. Catalase activity is elevated in heart, skeletal muscle, and brain. Cardiac mitochondria have 50 times higher catalase activity than in wild-type littermates leading to a delay in cardiac pathology. They also display improved cardiac performance with age, reducing their susceptibility to cardiac hypertrophy and failure. The severity of cataracts is reduced at 17 months of age, but rebounds to the level found in wildtype mice by 30 months of age. These MCAT mice also exhibit enhanced exercise performance, reduced age-dependent hearing loss, and reserved insulin sensitivity when fed a high-fat diet. When treated with the antiviral drug azidothymidine (AZT) they have a reduction in cardiomyopathy, and they show a reduction in MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced Parkinson's disease. H2O2 production and H2O2-induced aconitase inactivation are attenuated, and the development of mitochondrial deletions is reduced. These mice may be useful for studying the role of reactive oxygen species in mammalian longevity, as well as protection from lung adenocarcinoma.Development
The MCAT transgene was designed with the human Catalase (CAT) gene driven by a CMV enhancer/chicken beta-actin promoter (CAG; from the pCAGGS vector). The initiating methionine of CAT was deleted, and the first 25 amino acids of the ornithine transcarbamylase (Otc) leader sequence were added to the amino terminus to target this protein product to mitochondria. The transgene was microinjected into fertilized B6(B6C3F1) oocytes, and mice from founder line 4033 were bred to C57BL/6J mice. These mice were crossed to C57BL/6J mice for at least eight generations to establish a colony. In C57BL/6J mice, a naturally occurring deletion of exons 7-11 of the nicotinamide nucleotide transhydrogenase (Nnt) makes this strain more sensitive to oxidative challenge. For that reason, these mice have been crossed to C57BL/6NCrl mice to maintain an intact Nnt allele. Upon arrival at The Jackson Laboratory, transgenic mice were bred to C57BL/6NJ inbred mice (Stock No. 005304) to establish the colony.A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 005304 C57BL/6NJ | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (107 strains)
003333 C57BL/6-Tg(TF-CAT)48Gsa/J
Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
- Potential model based on transgenic expression of an ortholog of a human gene that is associated with this disease. Phenotypic similarity to the human disease has not been tested. Acatalasemia (CAT)
This mouse can be used to support research in many areas including:
Diabetes and Obesity Research
Type 1 Diabetes (IDDM)
resistant
Metabolism Research
Free Radical Research
Neurobiology Research
Alzheimer's Disease
Research Tools
Toxicology Research
free radical research
Sensorineural Research
Cataracts
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Tg(CAG-OTC/CAT)4033Prab | ||
|---|---|---|---|
| Allele Name | transgene insertion 4033, Peter S Rabinovitch | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) | MCAT; Tg(CAT)4033Wcl; | ||
| Strain of Origin | C57BL/6 x (C57BL/6 x C3H)F1 | ||
| Expressed Gene | CAT, catalase, human | ||
| Promoter | CMV, cytomegalovirus, human | ||
| Molecular Note | To generate the transgene, the 11 carboxy-terminal amino acids, including the peroxisomal localization signal, were deleted from the human catalase gene. The initiating methionine was also deleted and the first 25 amino acids of the ornithine transcarbamylase leader sequence were added to the amino terminus to target this protein product to mitochondria. The catalase cDNA construct was then cloned into a plasmid under the influence of the chicken-actin promoter/CMV enhancer (CAG). The catalase activity in the cardiac mitochondrial fraction of transgenic animals is 50 times higher than that in their wild-type littermates. [MGI Ref ID J:117831] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Tg(CAG-OTC/CAT)4033Prab, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Schriner SE; Linford NJ; Martin GM; Treuting P; Ogburn CE; Emond M; Coskun PE; Ladiges W; Wolf N; Van Remmen H; Wallace DC; Rabinovitch PS. 2005. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308(5730):1909-11. [PubMed: 15879174] [MGI Ref ID J:117831]
Additional References
Tg(CAG-OTC/CAT)4033Prab relatedDai DF; Hsieh EJ; Liu Y; Chen T; Beyer RP; Chin MT; MacCoss MJ; Rabinovitch PS. 2012. Mitochondrial proteome remodelling in pressure overload-induced heart failure: the role of mitochondrial oxidative stress. Cardiovasc Res 93(1):79-88. [PubMed: 22012956] [MGI Ref ID J:194879]
Dai DF; Johnson SC; Villarin JJ; Chin MT; Nieves-Cintron M; Chen T; Marcinek DJ; Dorn GW 2nd; Kang YJ; Prolla TA; Santana LF; Rabinovitch PS. 2011. Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Galphaq overexpression-induced heart failure. Circ Res 108(7):837-46. [PubMed: 21311045] [MGI Ref ID J:183593]
Mao P; Manczak M; Calkins MJ; Truong Q; Reddy TP; Reddy AP; Shirendeb U; Lo HH; Rabinovitch PS; Reddy PH. 2012. Mitochondria-targeted catalase reduces abnormal APP processing, amyloid beta production and BACE1 in a mouse model of Alzheimer's disease: implications for neuroprotection and lifespan extension. Hum Mol Genet 21(13):2973-90. [PubMed: 22492996] [MGI Ref ID J:184612]
Someya S; Xu J; Kondo K; Ding D; Salvi RJ; Yamasoba T; Rabinovitch PS; Weindruch R; Leeuwenburgh C; Tanokura M; Prolla TA. 2009. Age-related hearing loss in C57BL/6J mice is mediated by Bak-dependent mitochondrial apoptosis. Proc Natl Acad Sci U S A 106(46):19432-7. [PubMed: 19901338] [MGI Ref ID J:154747]
Swindell WR. 2009. Accelerated failure time models provide a useful statistical framework for aging research. Exp Gerontol 44(3):190-200. [PubMed: 19007875] [MGI Ref ID J:146582]
Vermulst M; Bielas JH; Kujoth GC; Ladiges WC; Rabinovitch PS; Prolla TA; Loeb LA. 2007. Mitochondrial point mutations do not limit the natural lifespan of mice. Nat Genet 39(4):540-3. [PubMed: 17334366] [MGI Ref ID J:141666]
West AP; Brodsky IE; Rahner C; Woo DK; Erdjument-Bromage H; Tempst P; Walsh MC; Choi Y; Shadel GS; Ghosh S. 2011. TLR signalling augments macrophage bactericidal activity through mitochondrial ROS. Nature 472(7344):476-80. [PubMed: 21525932] [MGI Ref ID J:172275]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX18
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, hemizygous mice may be bred to wildtype (non-carrier) mice from the colony or to C57BL/6NJ inbred mice (Stock No. 005304). Mating System Noncarrier x Hemizygote (Female x Male) 22-SEP-11 Hemizygote x Noncarrier (Female x Male) 22-SEP-11
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $232.00 Female or Male Hemizygous for Tg(CAG-OTC/CAT)4033Prab
Price per Pair (US dollars $) Pair Genotype $302.00 Hemizygous for Tg(CAG-OTC/CAT)4033Prab x Noncarrier $302.00 Noncarrier x Hemizygous for Tg(CAG-OTC/CAT)4033Prab Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $301.60 Female or Male Hemizygous for Tg(CAG-OTC/CAT)4033Prab
Price per Pair (US dollars $) Pair Genotype $392.60 Hemizygous for Tg(CAG-OTC/CAT)4033Prab x Noncarrier $392.60 Noncarrier x Hemizygous for Tg(CAG-OTC/CAT)4033Prab Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
|
|
|
Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
Control Information
| Control | ||
|---|---|---|
| Noncarrier | ||
| 005304 C57BL/6NJ | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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