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Updated: Jul 15, 2026
Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
Published on: March 23, 2015
Using MT(-/-) mice to study metallothionein and oxidative stress
C C Conrad1, D T Grabowski, C A Walter
1Department of Molecular Biology and Immunology, The University of North Texas Health Science Center at Fort Worth, Fort Worth, TX, USA.
Abstract:
Mice with null mutations for metallothionein genes MT-1 and MT-2 were used to study the role that metallothionein plays in protecting cellular targets in vivo from oxidative stress. Wild-type (MT(+/+)) and MT-null (MT(-/-)) mice were treated with either saline or zinc and exposed to two types of oxidative stress: gamma-irradiation or 2-nitropropane. There was no alteration in the antioxidant defense system (superoxide dismutase, catalase, or glutathione peroxidase and glutathione levels) to compensate for the lack of the metallothionein in the MT(-/-) mice. The amount of oxidative damage to liver DNA, lipids, and proteins were similar for the MT(-/-) and MT(+/+) mice even though the levels of metallothionein in the livers of the saline- or zinc-pretreated MT(+/+) mice were 5- to 100-fold greater than found in the MT(-/-) mice. To determine if metallothionein can protect mice from the lethal effects of ionizing radiation, the mean survivals of MT(-/-) and MT(+/+) mice exposed to whole body gamma-irradiation were measured and found to be similar. However, the mean survival increased significantly after zinc pretreatment for both the MT(-/-) and MT(+/+) mice. These results demonstrate that tissue levels of metallothionein do not protect mice in vivo against oxidative stress.
Insights
Metallothionein (MT) does not protect against oxidative stress in mice. MT-null mice showed similar damage and survival rates as wild-type mice, indicating MT is not essential for cellular protection in vivo.
Area of Science:
- Biochemistry
- Toxicology
- Genetics
Background:
- Metallothioneins (MTs) are proteins known for their role in metal binding and detoxification.
- Their potential role in protecting against oxidative stress in vivo is not fully understood.
Purpose of the Study:
- To investigate the protective role of metallothionein (MT) against oxidative stress in vivo.
- To determine if MT-1 and MT-2 gene null mutations affect cellular damage and survival following exposure to oxidative stressors.
Main Methods:
- Utilized wild-type (MT(+/+)) and MT-null (MT(-/-)) mice.
- Administered saline or zinc pretreatment.
- Exposed mice to gamma-irradiation or 2-nitropropane to induce oxidative stress.
- Assessed antioxidant defense systems, oxidative damage markers (DNA, lipids, proteins), and survival rates.
Main Results:
- MT-null mice showed no compensatory changes in other antioxidant systems.
- Oxidative damage levels were similar in MT(-/-) and MT(+/+) mice.
- MT(-/-) and MT(+/+) mice exhibited similar survival rates after irradiation, but zinc pretreatment improved survival in both groups.
Conclusions:
- Tissue metallothionein levels do not confer protection against oxidative stress in vivo.
- Zinc pretreatment enhances survival independently of metallothionein levels.
- MT-1 and MT-2 are not essential for protecting against the tested oxidative stressors.
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