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.
Peter S Rabinovitch, University of Washington
Genetic Background | Generation |
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?+N3
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Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
Starting at:
$255.00 Domestic price for female 4-week |
333.51 Domestic price for breeder pair |
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 and fertile. Catalase is 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.
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.
Expressed Gene | CAT, catalase, human |
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Site of Expression |
Allele Name | transgene insertion 4033, Peter S Rabinovitch |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | MCAT; Tg(CAT)4033Wcl |
Gene Symbol and Name | Tg(CAG-OTC/CAT)4033Prab, transgene insertion 4033, Peter S Rabinovitch |
Gene Synonym(s) | |
Promoter | CMV, cytomegalovirus, human |
Expressed Gene | CAT, catalase, human |
Strain of Origin | C57BL/6 x (C57BL/6 x C3H)F1 |
Chromosome | UN |
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. |
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).
When using the mCAT mouse strain in a publication, please cite the originating article(s) and include JAX stock #016197 in your Materials and Methods section.
Service/Product | Description | Price |
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Hemizygous or non carrier for Tg(CAG-OTC/CAT)4033Prab |
Frozen Mouse Embryo | B6.Cg-Tg(CAG-OTC/CAT)4033Prab/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Tg(CAG-OTC/CAT)4033Prab/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6.Cg-Tg(CAG-OTC/CAT)4033Prab/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6.Cg-Tg(CAG-OTC/CAT)4033Prab/J Frozen Embryo | $3373.50 |
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