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[Analysis of toxicity using metallothionein knockout mice]
1Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan. masahiko@dpc.agu.ac.jp
Abstract:
Two research groups produced metallothionein (MT)-I/II knockout mice with null mutation of MT-I and MT-II genes. In 1993, Choo et al. produced MT-I/II knockout mice with a mixed genetic background of 129 Ola and C57BL/6 strains. Palmiter et al. also produced MT-I/II knockout mice with a genetic background of 129/Sv strain in 1994. Subsequently, MT-I/II knockout mice have been used to clarify the biological function and physiological role of MT by many research groups. We were also provided MT-I/II knockout mice from Dr. Choo (Australia). F1 hybrid mice were mated with C57BL/6, and their offspring were back-crossed to C57BL/6 for ten generations. MT-I/II knockout (MT(-/-)) mice and wild-type (MT(+/+)) mice were obtained by mating of those heterozygous (MT(+/-)) mice. We have been investigating the susceptibility of MT-I/II knockout mice to toxicity of harmful factors and some diseases. Our present studies found that MT-I/II knockout mice have an increased sensitivity to harmful metals such as cadmium, mercury, and arsenic, oxidative stress, chemical carcinogenesis and neurodegenerative diseases. These results clearly indicate that MT plays an important role in defense of these toxicities. In this review, we present our findings and summarize recent reports with MT-I/II knockout mice concerning the role of MT as a biological protective factor.
Insights
Metallothionein (MT)-I/II knockout mice reveal MT's crucial role in defending against heavy metal toxicity, oxidative stress, and neurodegenerative diseases. These findings highlight MT as a key biological protective factor.
Area of Science:
- Biochemistry
- Toxicology
- Genetics
Context:
- Metallothioneins (MTs) are crucial proteins involved in metal homeostasis and detoxification.
- MT-I/II knockout mice models have been developed to elucidate the in vivo functions of MTs.
- Previous studies established MTs' role in protecting against heavy metal toxicity.
Purpose:
- To investigate the biological functions and physiological roles of metallothioneins (MTs) using MT-I/II knockout mice.
- To determine the susceptibility of MT-I/II knockout mice to various toxic agents and disease models.
- To summarize existing research and present new findings on MTs' protective functions.
Summary:
- MT-I/II knockout mice, generated through backcrossing, exhibit increased sensitivity to toxic metals (cadmium, mercury, arsenic), oxidative stress, chemical carcinogenesis, and neurodegenerative diseases.
- These findings confirm that MT plays a significant role in defending the body against these harmful factors.
- The study reviews current literature and presents novel data on MT-I/II knockout mice, emphasizing MT's protective capacity.
Impact:
- Provides clear evidence for the essential protective role of MT against a range of toxic insults.
- Establishes MT-I/II knockout mice as a valuable model for studying metal toxicity, oxidative stress, and related diseases.
- Advances the understanding of MT's biological significance in maintaining cellular and organismal health.
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