Strain Name:

B6.Cg-Tg(CAG-OTC/CAT)4033Prab/J

Stock Number:

016197

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
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

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 SystemNoncarrier x Hemizygote         (Female x Male)   22-SEP-11
Mating SystemHemizygote x Noncarrier         (Female x Male)   22-SEP-11
Specieslaboratory mouse
Generation?+n1f1 (12-DEC-13)
Generation Definitions
 
Donating 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

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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

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- 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)
View Research Applications

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

Cardiovascular Research

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 (Inserted expressed sequence)
Common Name(s) MCAT; Tg(CAT)4033Wcl;
Strain of OriginC57BL/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-alternate1,

MELT



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 related

Bartell SM; Kim HN; Ambrogini E; Han L; Iyer S; Serra Ucer S; Rabinovitch P; Jilka RL; Weinstein RS; Zhao H; O'Brien CA; Manolagas SC; Almeida M. 2014. FoxO proteins restrain osteoclastogenesis and bone resorption by attenuating H2O2 accumulation. Nat Commun 5:3773. [PubMed: 24781012]  [MGI Ref ID J:208828]

Dai 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]

Karamanlidis G; Lee CF; Garcia-Menendez L; Kolwicz SC Jr; Suthammarak W; Gong G; Sedensky MM; Morgan PG; Wang W; Tian R. 2013. Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. Cell Metab 18(2):239-50. [PubMed: 23931755]  [MGI Ref ID J:200989]

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 & HusbandryWhen 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 SystemNoncarrier 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 View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHemizygous for Tg(CAG-OTC/CAT)4033Prab  
Price per Pair (US dollars $)Pair Genotype
$304.00Hemizygous for Tg(CAG-OTC/CAT)4033Prab x Noncarrier  
$304.00Noncarrier x Hemizygous for Tg(CAG-OTC/CAT)4033Prab  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHemizygous for Tg(CAG-OTC/CAT)4033Prab  
Price per Pair (US dollars $)Pair Genotype
$395.20Hemizygous for Tg(CAG-OTC/CAT)4033Prab x Noncarrier  
$395.20Noncarrier x Hemizygous for Tg(CAG-OTC/CAT)4033Prab  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Noncarrier
   005304 C57BL/6NJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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.
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JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED “AS IS”. JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.


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