PMID:15721235

Citation	Goldberg, MS, Pisani, A, Haburcak, M, Vortherms, TA, Kitada, T, Costa, C, Tong, Y, Martella, G, Tscherter, A, Martins, A, Bernardi, G, Roth, BL, Pothos, EN, Calabresi, P and Shen, J (2005) Nigrostriatal dopaminergic deficits and hypokinesia caused by inactivation of the familial Parkinsonism-linked gene DJ-1. Neuron 45:489-96
Abstract	The manifestations of Parkinson's disease are caused by reduced dopaminergic innervation of the striatum. Loss-of-function mutations in the DJ-1 gene cause early-onset familial parkinsonism. To investigate a possible role for DJ-1 in the dopaminergic system, we generated a mouse model bearing a germline disruption of DJ-1. Although DJ-1(-/-) mice had normal numbers of dopaminergic neurons in the substantia nigra, evoked dopamine overflow in the striatum was markedly reduced, primarily as a result of increased reuptake. Nigral neurons lacking DJ-1 were less sensitive to the inhibitory effects of D2 autoreceptor stimulation. Corticostriatal long-term potentiation was normal in medium spiny neurons of DJ-1(-/-) mice, but long-term depression (LTD) was absent. The LTD deficit was reversed by treatment with D2 but not D1 receptor agonists. Furthermore, DJ-1(-/-) mice displayed hypoactivity in the open field. Collectively, our findings suggest an essential role for DJ-1 in dopaminergic physiology and D2 receptor-mediated functions.
Links	PubMed Online version:10.1016/j.neuron.2005.01.041
Keywords	2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology; Age Factors; Animals; Behavior, Animal; Blotting, Southern/methods; Blotting, Western/methods; Cell Count; Cerebral Cortex/cytology; Cerebral Cortex/physiology; Disease Models, Animal; Dopamine/deficiency; Dopamine Agonists/pharmacology; Dopamine Plasma Membrane Transport Proteins; Electric Stimulation/methods; Electrochemistry/methods; Excitatory Postsynaptic Potentials/drug effects; Excitatory Postsynaptic Potentials/physiology; Germ-Line Mutation; Humans; Hypokinesia/physiopathology; Immunohistochemistry/methods; Intracellular Signaling Peptides and Proteins; Membrane Glycoproteins/metabolism; Membrane Transport Proteins/metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins/metabolism; Neurons/physiology; Oncogene Proteins/physiology; Parkinsonian Disorders/genetics; Parkinsonian Disorders/metabolism; Quinpirole/pharmacology; RNA, Messenger/biosynthesis; Radioligand Assay/methods; Receptors, Dopamine D2/metabolism; Reverse Transcriptase Polymerase Chain Reaction/methods; Substantia Nigra/cytology; Substantia Nigra/drug effects; Substantia Nigra/metabolism; Tyrosine 3-Monooxygenase/metabolism
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.