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Analysis of targeted mutation in DJ-1 on cellular function in primary astrocytes

Analysis of targeted mutation in DJ-1 on cellular function in primary astrocytes
DJ-1 mutation induces early-onset Parkinson's disease, and conversely over-expression of DJ-1 is associated with cancer in numerous tissues. A gene-trap screening library conducted in embryonic stem cells was utilized for generation of a DJ-1 mutant mouse. Real-time PCR and immunoblotting were utilized to confirm functional mutation of the DJ-1 gene. Normal DJ-1 protein expression in adult mouse tissue was characterized and demonstrates high expression in brain tissue with wide systemic distribution. Primary astrocytes isolated from DJ-1(-/-) mice reveal a decreased nuclear localization of DJ-1 protein in response to rotenone or LPS, with a concomitant increase in mitochondrial localization of DJ-1 found only in the rotenone exposure. Resting mitochondrial membrane potential was significantly lower in DJ-1(-/-) astrocytes, as compared to controls. Our DJ-1 knockout mouse provides an exciting tool for exploring the molecular and physiological roles of DJ-1 to further explicate its functions in neurodegeneration.
- Colorado State University United States
Cell Nucleus, Cerebral Cortex, Lipopolysaccharides, Membrane Potential, Mitochondrial, Mice, Knockout, Oncogene Proteins, Dose-Response Relationship, Drug, Genotype, Protein Deglycase DJ-1, Peroxiredoxins, Mitochondria, Mice, Protein Transport, Phenotype, Astrocytes, Rotenone, Mutation, Animals, Cells, Cultured
Cell Nucleus, Cerebral Cortex, Lipopolysaccharides, Membrane Potential, Mitochondrial, Mice, Knockout, Oncogene Proteins, Dose-Response Relationship, Drug, Genotype, Protein Deglycase DJ-1, Peroxiredoxins, Mitochondria, Mice, Protein Transport, Phenotype, Astrocytes, Rotenone, Mutation, Animals, Cells, Cultured
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