Development of Animal Models of Drug‐Induced Mitochondrial Toxicity

Boelsterli, Urs A.; Lee, Yie Hou

doi:10.1002/9780470372531.ch23

Cited by 2 publications

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“…This implies that the singular loss of the Sod2 allele results in a subtle redox imbalance. The data confirm biochemical and functional findings from earlier studies and are compatible with the hypothesis that the Sod2 1/2 mouse is a suitable animal model for clinically silent mitochondrial abnormalities that can result in mild oxidative stress in mitochondria [14]. It has been generally recognized that heterozygous mutants could lead to interesting and novel genetic mouse models beyond knockout mice because such mice display partial-intermediate phenotypes [48].…”

Section: Discussionsupporting

confidence: 90%

“…Because the Sod2 1/2 mouse model has been increasingly utilized in pharmacological/toxicological research [14], it is important that the consequences of the deleted gene be thoroughly characterized not only with respect to gross pathology and functional changes, but also at the molecular level. Specifically, a global characterization of gene expression at the post-transcriptional level would be important.…”

Section: Introductionmentioning

confidence: 99%

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Proteomics profiling of hepatic mitochondria in heterozygous Sod2^+/− mice, an animal model of discreet mitochondrial oxidative stress

et al. 2008

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The heterozygous superoxide dismutase 2 (SOD2) gene knockout (Sod2+/-) mouse model has been increasingly used in cardiovascular and age research, neurobiology, and pharmacology/toxicology. These mutant mice exhibit mild oxidant stress in mitochondria but remain clinically inconspicuous. Although the Sod2+/- mouse has been characterized with respect to mitochondrial function and transcript expression of certain individual genes, the effects of the singular loss of the Sod2 allele on the global expression of hepatic mitochondrial proteins remains unknown. We therefore performed a differential analysis of the hepatic mitochondrial proteome from Sod2+/- mice and wild-type mice in order to identify the consequences of partial Sod2 deletion. Using 2-D difference gel electrophoresis (DIGE) coupled with MALDI-MS/MS, we found approximately 1500 protein spots, of which 57 were differentially expressed (> or =1.5-fold change). Both SOD 1 and 2 were downregulated, but other antioxidant enzymes and related proteins were upregulated (

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Proteomics profiling of hepatic mitochondria in heterozygous Sod2^+/− mice, an animal model of discreet mitochondrial oxidative stress

et al. 2008

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The Sod2 mutant mouse as a model for oxidative stress: A functional proteomics perspective

Lee

Lin

Boelsterli

et al. 2009

Mass Spectrometry Reviews

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Oxidative stress has been implicated in the pathogenesis of numerous human diseases and disorders, but the mechanistic basis often remains enigmatic. The Sod2 mutant mouse, which is sensitized to mitochondrial stress, is an ideal mutant model for studying the role of oxidative stress in a diverse range of complications arising from mitochondrial dysfunction and diminished antioxidant defense. To fully appreciate the widespread molecular consequences under increased oxidative stress, a systems approach utilizing proteomics is able to provide a global overview of the complex biological changes, which a targeted single biomolecular approach cannot address fully. This review focuses on the applications of mass spectrometry and functional proteomics in the Sod2 mouse. The combinatorial approach provides novel insights into the interplay of chemistry and biology, free radicals and proteins, thereby augmenting our understanding of how redox perturbations influence protein dynamics. Ultimately, this knowledge can lead to the development of free radical-targeted therapies.

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Development of Animal Models of Drug‐Induced Mitochondrial Toxicity

Cited by 2 publications

References 52 publications

Proteomics profiling of hepatic mitochondria in heterozygous Sod2^+/− mice, an animal model of discreet mitochondrial oxidative stress

Proteomics profiling of hepatic mitochondria in heterozygous Sod2^+/− mice, an animal model of discreet mitochondrial oxidative stress

The Sod2 mutant mouse as a model for oxidative stress: A functional proteomics perspective

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Development of Animal Models of Drug‐Induced Mitochondrial Toxicity

Cited by 2 publications

References 52 publications

Proteomics profiling of hepatic mitochondria in heterozygous Sod2+/− mice, an animal model of discreet mitochondrial oxidative stress

Proteomics profiling of hepatic mitochondria in heterozygous Sod2+/− mice, an animal model of discreet mitochondrial oxidative stress

The Sod2 mutant mouse as a model for oxidative stress: A functional proteomics perspective

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Proteomics profiling of hepatic mitochondria in heterozygous Sod2^+/− mice, an animal model of discreet mitochondrial oxidative stress

Proteomics profiling of hepatic mitochondria in heterozygous Sod2^+/− mice, an animal model of discreet mitochondrial oxidative stress