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Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function
Loss-of-function mutations in the DJ-1 gene account for an autosomal recessive form of Parkinson's disease (PD). To investigate the physiological functions of DJ-1 in vivo, we generated DJ-1 knockout (DJ-1−/−) mice. Younger (<1 year) DJ-1−/− mice were hypoactive and had mild gait abnormaliti...
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| Izdano u: | Neurobiology of Disease |
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| Glavni autori: | , , , , , , , , , , , , , |
| Format: | Članak |
| Izdano: |
Elsevier
2008-03-01
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| Teme: | |
| Online pristup: | http://www.sciencedirect.com/science/article/pii/S0969996107002604 |
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| Sažetak: | Loss-of-function mutations in the DJ-1 gene account for an autosomal recessive form of Parkinson's disease (PD). To investigate the physiological functions of DJ-1 in vivo, we generated DJ-1 knockout (DJ-1−/−) mice. Younger (<1 year) DJ-1−/− mice were hypoactive and had mild gait abnormalities. Older DJ-1−/−, however, showed decreased body weight and grip strength and more severe gait irregularities compared to wild-type littermates. The basal level of extracellular dopamine, evoked dopamine release and dopamine receptor D2 sensitivity appeared normal in the striatum of DJ-1−/− mice, which was consistent with similar results between DJ-1−/− and controls in behavioral paradigms specific for the dopaminergic system. An examination of spinal cord, nerve and muscle tissues failed to identify any pathological changes that were consistent with the noted motor deficits. Taken together, our findings suggest that loss of DJ-1 leads to progressive behavioral changes without significant alterations in nigrostriatal dopaminergic and spinal motor systems. |
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| ISSN: | 1095-953X |