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 Crawley, Toni Shippenberg, Huaibin Cai

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)505-514
Number of pages10
JournalNeurobiology of Disease
Volume29
Issue number3
DOIs
StatePublished - Mar 2008
Externally publishedYes

Keywords

  • DJ-1
  • Dopamine
  • Knockout mouse
  • Motor behavior
  • Muscle
  • Parkinson's disease
  • Spinal cord
  • Striatum

ASJC Scopus subject areas

  • Neurology

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  • Cite this

    Chandran, J. S., Lin, X., Zapata, A., Höke, A., Shimoji, M., Moore, S. O. L., Galloway, M. P., Laird, F. M., Wong, P. C., Price, D. L., Bailey, K. R., Crawley, J., Shippenberg, T., & Cai, H. (2008). Progressive behavioral deficits in DJ-1-deficient mice are associated with normal nigrostriatal function. Neurobiology of Disease, 29(3), 505-514. https://doi.org/10.1016/j.nbd.2007.11.011