Differential involvement of striosome and matrix dopamine systems in a transgenic model of dopa-responsive dystonia

Kenta Sato, Chiho Sumi-Ichinose, Ryuji Kaji, Kazuhisa Ikemoto, Takahide Nomura, Ikuko Nagatsu, Hiroshi Ichinose, Masayuki Ito, Wataru Sako, Shinji Nagahiro, Ann M. Graybiel, Satoshi Goto

Research output: Contribution to journalArticlepeer-review

82 Citations (Scopus)


Dopa-responsive dystonia (DRD) is a hereditary dystonia characterized by a childhood onset of fixed dystonic posture with a dramatic and sustained response to relatively low doses of levodopa. DRD is thought to result from striatal dopamine deficiency due to a reduced synthesis and activity of tyrosine hydroxylase (TH), the synthetic enzyme for dopamine. The mechanisms underlying the genesis of dystonia in DRD present a challenge to models of basal ganglia movement control, given that striatal dopamine deficiency is the hallmark of Parkinson's disease. We report here behavioral and anatomical observations on a transgenic mouse model for DRD in which the gene for 6-pyruvoyl-tetrahydropterin synthase is targeted to render selective dysfunction of TH synthesis in the striatum. Mutant mice exhibited motor deficits phenotypically resembling symptoms of human DRD and manifested a major depletion of TH labeling in the striatum, with a marked posterior-to-anterior gradient resulting in near total loss caudally. Strikingly, within the regions of remaining TH staining in the striatum, there was a greater loss of TH labeling in striosomes than in the surrounding matrix. The predominant loss of TH expression in striosomes occurred during the early postnatal period, when motor symptoms first appeared. We suggest that the differential striosome-matrix pattern of dopamine loss could be a key to identifying the mechanisms underlying the genesis of dystonia in DRD.

Original languageEnglish
Pages (from-to)12551-12556
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number34
Publication statusPublished - 26-08-2008

All Science Journal Classification (ASJC) codes

  • General


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