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Causative mutations are located in a noncoding region of the TATA\u2010box binding protein\u2010associated factor 1 (<jats:italic>TAF1<\/jats:italic>) gene and result in aberrant splicing. There are 2 major TAF1 isoforms that may be decreased in symptomatic patients, including the ubiquitously expressed canonical cTAF1 and the neuronal\u2010specific nTAF1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this study was to determine the behavioral and transcriptomic effects of decreased cTAF1 and\/or nTAF1 in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We generated adeno\u2010associated viral (AAV) vectors encoding microRNAs targeting <jats:italic>Taf1<\/jats:italic> in a splice\u2010isoform selective manner. We performed intracerebroventricular viral injections in newborn mice and rats and intrastriatal infusions in 3\u2010week\u2010old rats. The effects of <jats:italic>Taf1<\/jats:italic> knockdown were assayed at 4\u2009months of age with evaluation of motor function, histology, and RNA sequencing of the striatum, followed by its validation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report motor deficits in all cohorts, more pronounced in animals injected at P0, in which we also identified transcriptomic alterations in multiple neuronal pathways, including the cholinergic synapse. In both species, we show a reduced number of striatal cholinergic interneurons and their marker mRNAs after <jats:italic>Taf1<\/jats:italic> knockdown in the newborn.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study provides novel information regarding the requirement for TAF1 in the postnatal maintenance of striatal cholinergic neurons, the dysfunction of which is involved in other inherited forms of dystonia. \u00a9 2021 International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28750","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T08:57:29Z","timestamp":1629190649000},"page":"2780-2794","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Striatal Cholinergic Dysregulation after Neonatal Decrease in X\u2010Linked Dystonia Parkinsonism\u2010Related <scp>TAF1<\/scp> Isoforms"],"prefix":"10.1002","volume":"36","author":[{"given":"Maria\u2010Daniela","family":"Cirnaru","sequence":"first","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Creus\u2010Muncunill","sequence":"additional","affiliation":[{"name":"Department of Neurology Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shareen","family":"Nelson","sequence":"additional","affiliation":[{"name":"Raymond G. 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