Catalase transgenic mice: Characterization and sensitivity to oxidative stress

Xinlian Chen; Hanyu Liang; Holly Van Remmen; Jan Vijg; Arlan Richardson

doi:10.1016/j.abb.2003.12.023

Catalase transgenic mice: Characterization and sensitivity to oxidative stress

Xinlian Chen, Hanyu Liang, Holly Van Remmen, Jan Vijg, Arlan Richardson

Research output: Contribution to journal › Article › peer-review

63 Scopus citations

Abstract

The role of catalase in the antioxidant defense system was studied using transgenic mice [Tg(CAT)] harboring a human genomic clone containing the entire human CAT gene. Catalase activity was 2-fold higher in the tissues of hemizygous [Tg(CAT)^+/o] mice and 3- to 4-fold higher in the tissues of homozygous [Tg(CAT)^+/+] mice compared to wild type mice. The human CAT transgene was expressed in a tissue-specific pattern that was similar to the endogenous catalase gene. The levels of other major antioxidant enzymes were not altered in the tissues of the transgenic mice. Hepatocytes and fibroblasts from the Tg(CAT)^+/+ mice were more resistant to hydrogen peroxide-induced cell death but were more sensitive to paraquat and TNFα toxicity. Fibroblasts from the Tg(CAT)^+/+ mice showed reduced growth rate in culture without treatment and reduced colony-forming capability after γ-irradiation compared to fibroblasts from wild type mice. In addition, the Tg(CAT)^+/+ animals were more sensitive to γ-irradiation.

Original language	English (US)
Pages (from-to)	197-210
Number of pages	14
Journal	Archives of Biochemistry and Biophysics
Volume	422
Issue number	2
DOIs	https://doi.org/10.1016/j.abb.2003.12.023
State	Published - Feb 15 2004
Externally published	Yes

Keywords

Antioxidant enzymes
Catalase
Oxidative stress
Transgenic mice

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology

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10.1016/j.abb.2003.12.023

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title = "Catalase transgenic mice: Characterization and sensitivity to oxidative stress",

abstract = "The role of catalase in the antioxidant defense system was studied using transgenic mice [Tg(CAT)] harboring a human genomic clone containing the entire human CAT gene. Catalase activity was 2-fold higher in the tissues of hemizygous [Tg(CAT)+/o] mice and 3- to 4-fold higher in the tissues of homozygous [Tg(CAT)+/+] mice compared to wild type mice. The human CAT transgene was expressed in a tissue-specific pattern that was similar to the endogenous catalase gene. The levels of other major antioxidant enzymes were not altered in the tissues of the transgenic mice. Hepatocytes and fibroblasts from the Tg(CAT)+/+ mice were more resistant to hydrogen peroxide-induced cell death but were more sensitive to paraquat and TNFα toxicity. Fibroblasts from the Tg(CAT)+/+ mice showed reduced growth rate in culture without treatment and reduced colony-forming capability after γ-irradiation compared to fibroblasts from wild type mice. In addition, the Tg(CAT)+/+ animals were more sensitive to γ-irradiation.",

keywords = "Antioxidant enzymes, Catalase, Oxidative stress, Transgenic mice",

author = "Xinlian Chen and Hanyu Liang and {Van Remmen}, Holly and Jan Vijg and Arlan Richardson",

note = "Funding Information: This work was supported by a Merit grant and a Environmental Hazards Center grant from the Department of Veteran Affairs, NIA-funded Program Project Grants (PO1 AG14674 and PO1 AG020591), and the Nathan Shock Center of Excellence in Basic Biology of Aging (PO3 AG13319) at the University of Texas Health Science Center at San Antonio.",

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AU - Van Remmen, Holly

AU - Vijg, Jan

AU - Richardson, Arlan

N1 - Funding Information: This work was supported by a Merit grant and a Environmental Hazards Center grant from the Department of Veteran Affairs, NIA-funded Program Project Grants (PO1 AG14674 and PO1 AG020591), and the Nathan Shock Center of Excellence in Basic Biology of Aging (PO3 AG13319) at the University of Texas Health Science Center at San Antonio.

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N2 - The role of catalase in the antioxidant defense system was studied using transgenic mice [Tg(CAT)] harboring a human genomic clone containing the entire human CAT gene. Catalase activity was 2-fold higher in the tissues of hemizygous [Tg(CAT)+/o] mice and 3- to 4-fold higher in the tissues of homozygous [Tg(CAT)+/+] mice compared to wild type mice. The human CAT transgene was expressed in a tissue-specific pattern that was similar to the endogenous catalase gene. The levels of other major antioxidant enzymes were not altered in the tissues of the transgenic mice. Hepatocytes and fibroblasts from the Tg(CAT)+/+ mice were more resistant to hydrogen peroxide-induced cell death but were more sensitive to paraquat and TNFα toxicity. Fibroblasts from the Tg(CAT)+/+ mice showed reduced growth rate in culture without treatment and reduced colony-forming capability after γ-irradiation compared to fibroblasts from wild type mice. In addition, the Tg(CAT)+/+ animals were more sensitive to γ-irradiation.

AB - The role of catalase in the antioxidant defense system was studied using transgenic mice [Tg(CAT)] harboring a human genomic clone containing the entire human CAT gene. Catalase activity was 2-fold higher in the tissues of hemizygous [Tg(CAT)+/o] mice and 3- to 4-fold higher in the tissues of homozygous [Tg(CAT)+/+] mice compared to wild type mice. The human CAT transgene was expressed in a tissue-specific pattern that was similar to the endogenous catalase gene. The levels of other major antioxidant enzymes were not altered in the tissues of the transgenic mice. Hepatocytes and fibroblasts from the Tg(CAT)+/+ mice were more resistant to hydrogen peroxide-induced cell death but were more sensitive to paraquat and TNFα toxicity. Fibroblasts from the Tg(CAT)+/+ mice showed reduced growth rate in culture without treatment and reduced colony-forming capability after γ-irradiation compared to fibroblasts from wild type mice. In addition, the Tg(CAT)+/+ animals were more sensitive to γ-irradiation.

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Catalase transgenic mice: Characterization and sensitivity to oxidative stress

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