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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2008-03-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996107002604 |
| _version_ | 1819161064297725952 |
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| author | Jayanth S. Chandran Xian Lin Agustin Zapata Ahmet Höke Mika Shimoji Shonagh O'Leary Moore Matthew P. Galloway Fiona M. Laird Philip C. Wong Donald L. Price Kathleen R. Bailey Jacqueline N. Crawley Toni Shippenberg Huaibin Cai |
| author_facet | Jayanth S. Chandran Xian Lin Agustin Zapata Ahmet Höke Mika Shimoji Shonagh O'Leary Moore Matthew P. Galloway Fiona M. Laird Philip C. Wong Donald L. Price Kathleen R. Bailey Jacqueline N. Crawley Toni Shippenberg Huaibin Cai |
| author_sort | Jayanth S. Chandran |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T17:06:24Z |
| format | Article |
| id | doaj.art-df399a00a978488ebc81c32f71b401bb |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T17:06:24Z |
| publishDate | 2008-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-df399a00a978488ebc81c32f71b401bb2022-12-21T18:19:11ZengElsevierNeurobiology of Disease1095-953X2008-03-01293505514Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal functionJayanth S. Chandran0Xian Lin1Agustin Zapata2Ahmet Höke3Mika Shimoji4Shonagh O'Leary Moore5Matthew P. Galloway6Fiona M. Laird7Philip C. Wong8Donald L. Price9Kathleen R. Bailey10Jacqueline N. Crawley11Toni Shippenberg12Huaibin Cai13Unit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A116, MSC 3707, 35 Convent Drive, Bethesda, MD 20892, USA; Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USAUnit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A116, MSC 3707, 35 Convent Drive, Bethesda, MD 20892, USAIntegrative Neuroscience Section, National Institute of Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USADepartment of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21025, USAUnit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A116, MSC 3707, 35 Convent Drive, Bethesda, MD 20892, USADepartment of Psychiatry and Behavioral Neurosciences and Anesthesiology, Wayne State University, Detroit, MI 48201, USADepartment of Psychiatry and Behavioral Neurosciences and Anesthesiology, Wayne State University, Detroit, MI 48201, USADepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21025, USADepartment of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21025, USADepartment of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA; Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21025, USALaboratory of Behavioral Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USALaboratory of Behavioral Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USAIntegrative Neuroscience Section, National Institute of Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USAUnit of Transgenesis, Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Building 35, Room 1A116, MSC 3707, 35 Convent Drive, Bethesda, MD 20892, USA; Corresponding author. Fax: +1 301 480 2830.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.http://www.sciencedirect.com/science/article/pii/S0969996107002604DJ-1Knockout mouseParkinson's diseaseDopamineStriatumSpinal cord |
| spellingShingle | Jayanth S. Chandran Xian Lin Agustin Zapata Ahmet Höke Mika Shimoji Shonagh O'Leary Moore Matthew P. Galloway Fiona M. Laird Philip C. Wong Donald L. Price Kathleen R. Bailey Jacqueline N. Crawley Toni Shippenberg Huaibin Cai Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function Neurobiology of Disease DJ-1 Knockout mouse Parkinson's disease Dopamine Striatum Spinal cord |
| title | Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function |
| title_full | Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function |
| title_fullStr | Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function |
| title_full_unstemmed | Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function |
| title_short | Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function |
| title_sort | progressive behavioral deficits in dj 1 deficient mice are associated with normal nigrostriatal function |
| topic | DJ-1 Knockout mouse Parkinson's disease Dopamine Striatum Spinal cord |
| url | http://www.sciencedirect.com/science/article/pii/S0969996107002604 |
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