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

被引：24

作者：

Ashley, Amanda K. ^{[2
]}

Hanneman, William H. ^{[1
,2
]}

Katoh, Takeshi ^{[1
]}

Moreno, Julie A. ^{[2
]}

Pollack, Ashley ^{[1
]}

Tjalkens, Ronald B. ^{[1
,2
]}

Legare, Marie E. ^{[1
,2
]}

机构：

[1] Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA

[2] Colorado State Univ, Cell & Mol Biol Grad Program, Ft Collins, CO 80523 USA

来源：

TOXICOLOGY LETTERS | 2009年 / 184卷 / 03期

关键词：

DJ-1; Parkinson's disease; Gene-trap; Mitochondria; TUMOR-NECROSIS-FACTOR; EARLY-ONSET PARKINSONISM; ALPHA-SYNUCLEIN; ANTIOXIDATIVE STRESS; OXIDATIVE STRESS; PROTEIN DJ-1; DISEASE; EXPOSURE; LIPOPOLYSACCHARIDE; GENE;

D O I：

10.1016/j.toxlet.2008.11.008

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

引用

页码：186 / 191

页数：6

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