Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function

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

Neurobiology of Disease (Mar 2008)

Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function

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

Affiliations

Jayanth S. Chandran: Unit 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, USA
Xian Lin: Unit 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
Agustin Zapata: Integrative Neuroscience Section, National Institute of Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA
Ahmet Höke: Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA
Mika Shimoji: Unit 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
Shonagh O'Leary Moore: Department of Psychiatry and Behavioral Neurosciences and Anesthesiology, Wayne State University, Detroit, MI 48201, USA
Matthew P. Galloway: Department of Psychiatry and Behavioral Neurosciences and Anesthesiology, Wayne State University, Detroit, MI 48201, USA
Fiona M. Laird: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA
Philip C. Wong: Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21025, USA
Donald L. Price: Department 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, USA
Kathleen R. Bailey: Laboratory of Behavioral Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USA
Jacqueline N. Crawley: Laboratory of Behavioral Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USA
Toni Shippenberg: Integrative Neuroscience Section, National Institute of Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA
Huaibin Cai: Unit 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.

Journal volume & issue: Vol. 29, no. 3
pp. 505 – 514

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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