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 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.
Chandran
Jayanth S
JS
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.
Lin
Xian
X
Zapata
Agustin
A
Höke
Ahmet
A
Shimoji
Mika
M
Moore
Shonagh O'Leary
SO
Galloway
Matthew P
MP
Laird
Fiona M
FM
Wong
Philip C
PC
Price
Donald L
DL
Bailey
Kathleen R
KR
Crawley
Jacqueline N
JN
Shippenberg
Toni
T
Cai
Huaibin
H
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology*; D018450:Disease Progression; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics*; D009043:Motor Activity / Q000502:physiology; D013378:Substantia Nigra / Q000502:physiology*
D008869:Microtubule-Associated Proteins; C491282:SP22 protein, mouse