{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:51:25Z","timestamp":1789620685532,"version":"build-2803163510"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"34","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,8,26]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1073\/pnas.0806065105","type":"journal-article","created":{"date-parts":[[2008,8,19]],"date-time":"2008-08-19T23:52:10Z","timestamp":1219189930000},"page":"12551-12556","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":84,"title":["Differential involvement of striosome and matrix dopamine systems in a transgenic model of dopa-responsive dystonia"],"prefix":"10.1073","volume":"105","author":[{"given":"Kenta","family":"Sato","sequence":"first","affiliation":[{"name":"*Department of Clinical Neuroscience, Institute of Health Biosciences, Graduate School of Medicine, University of Tokushima, Tokushima 770-8503, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiho","family":"Sumi-Ichinose","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Kaji","sequence":"additional","affiliation":[{"name":"*Department of Clinical Neuroscience, Institute of Health Biosciences, Graduate School of Medicine, University of Tokushima, Tokushima 770-8503, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Ikemoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahide","family":"Nomura","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuko","family":"Nagatsu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Ichinose","sequence":"additional","affiliation":[{"name":"Department of Life Science, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8501, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayuki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Sako","sequence":"additional","affiliation":[{"name":"*Department of Clinical Neuroscience, Institute of Health Biosciences, Graduate School of Medicine, University of Tokushima, Tokushima 770-8503, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Nagahiro","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Institute of Health Biosciences, Graduate School of Medicine, University of Tokushima, Tokushima 770-8503, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Graybiel","sequence":"additional","affiliation":[{"name":"**McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Goto","sequence":"additional","affiliation":[{"name":"*Department of Clinical Neuroscience, Institute of Health Biosciences, Graduate School of Medicine, University of Tokushima, Tokushima 770-8503, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,8,26]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(02)00137-0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.58.12.1839"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.59.8.1183"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(08)70022-X"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1194-236"},{"key":"e_1_3_3_6_2","first-page":"253","article-title":"Dystonias responding to levodopa and failure in biopterin metabolism","volume":"78","author":"Nomura Y","year":"1998","unstructured":"Y Nomura, et al., Dystonias responding to levodopa and failure in biopterin metabolism. 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