Decreased dopamine receptor 1 activity and impaired motor-skill transfer in Dyt1 ΔGAG heterozygous knock-in mice.

ABSTRACT: DYT1 dystonia is a movement disorder caused by a trinucleotide deletion (ΔGAG) in DYT1 (TOR1A), corresponding to a glutamic acid loss in the C-terminal region of torsinA. Functional alterations in the basal ganglia circuits have been reported in both DYT1 dystonia patients and rodent models. Dyt1 ΔGAG heterozygous knock-in (KI) mice exhibit motor deficits and decreased striatal dopamine receptor 2 (D2R) binding activity, suggesting a malfunction of the indirect pathway. However, the role of the direct pathway in pathogenesis of dystonia is not yet clear. Here, we report that Dyt1 KI mice exhibit significantly decreased striatal dopamine receptor 1 (D1R) binding activity and D1R protein levels, suggesting the alteration of the direct pathway. The decreased D1R may be caused by translational

SUBMITTER: Yokoi F 

PROVIDER: S-EPMC4286880 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature