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PMID:15799973
| Citation |
Chen, L, Cagniard, B, Mathews, T, Jones, S, Koh, HC, Ding, Y, Carvey, PM, Ling, Z, Kang, UJ and Zhuang, X (2005) Age-dependent motor deficits and dopaminergic dysfunction in DJ-1 null mice. J. Biol. Chem. 280:21418-26 |
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| Abstract |
Mutations in the DJ-1 gene were recently identified in an autosomal recessive form of early-onset familial Parkinson disease. Structural biology, biochemistry, and cell biology studies have suggested potential functions of DJ-1 in oxidative stress, protein folding, and degradation pathways. However, animal models are needed to determine whether and how loss of DJ-1 function leads to Parkinson disease. We have generated DJ-1 null mice with a mutation that resembles the large deletion mutation reported in patients. Our behavioral analyses indicated that DJ-1 deficiency led to age-dependent and task-dependent motoric behavioral deficits that are detectable by 5 months of age. Unbiased stereological studies did not find obvious dopamine neuron loss in 6-month- and 11-month-old mice. Neurochemical examination revealed significant changes in striatal dopaminergic function consisting of increased dopamine reuptake rates and elevated tissue dopamine content. These data represent the in vivo evidence that loss of DJ-1 function alters nigrostriatal dopaminergic function and produces motor deficits. |
| Links |
PubMed Online version:10.1074/jbc.M413955200 |
| Keywords |
Age Factors; Aging; Animals; Blotting, Western; Brain/metabolism; Chromatography, High Pressure Liquid; Disease Models, Animal; Dopamine/metabolism; Dopamine/pharmacokinetics; Electrochemistry; Female; Gene Targeting; Genotype; Immunohistochemistry; Male; Mice; Mice, Mutant Strains; Mice, Transgenic; Microscopy, Fluorescence; Mutation; Neurons/metabolism; Oxidative Stress; Parkinson Disease/genetics; Protein Folding; Proteins/chemistry; Time Factors; Tyrosine 3-Monooxygenase/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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References
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