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

Document Type

Article

Abstract

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.

Medical Subject Headings

Animals; Astrocytes (drug effects, metabolism); Cell Nucleus (metabolism); Cells, Cultured; Cerebral Cortex (drug effects, metabolism); Dose-Response Relationship, Drug; Genotype; Lipopolysaccharides (pharmacology); Membrane Potential, Mitochondrial; Mice; Mice, Knockout; Mitochondria (metabolism); Mutation; Oncogene Proteins (genetics, metabolism); Peroxiredoxins; Phenotype; Protein Deglycase DJ-1; Protein Transport; Rotenone (pharmacology)

Publication Date

2-10-2009

Publication Title

Toxicology letters

ISSN

0378-4274

Volume

184

Issue

3

First Page

186

Last Page

91

PubMed ID

19063952

Digital Object Identifier (DOI)

10.1016/j.toxlet.2008.11.008

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