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Because the validation of new animal models is essential for the understanding of the aetiology and pathophysiology of movement disorders, the objective was to characterise motoric phenotype in\n CYP2C19<\/jats:italic>\n transgenic mice and to investigate its validity as a new animal model of ataxia.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The rotarod, paw\u2010print and beam\u2010walking tests were utilised to characterise the motoric phenotype. The volumes of 20 brain regions in\n CYP2C19<\/jats:italic>\n transgenic and wild\u2010type mice were quantified by 9.4T gadolinium\u2010enhanced\n post\u2010mortem<\/jats:italic>\n structural neuroimaging. Antioxidative enzymatic activity was quantified biochemically. Dopaminergic alterations were characterised by chromatographic quantification of concentrations of dopamine and its metabolites and by subsequent immunohistochemical analyses. The beam\u2010walking test was repeated after the treatment with dopamine receptor antagonists ecopipam and raclopride.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n CYP2C19<\/jats:italic>\n transgenic mice exhibit abnormal, unilateral ataxia\u2010like gait, clasping reflex and 5.6\u2010fold more paw\u2010slips in the beam\u2010walking test; the motoric phenotype was more pronounced in youth. Transgenic mice exhibited a profound reduction of 12% in cerebellar volume and a moderate reduction of 4% in hippocampal volume; both regions exhibited an increased antioxidative enzyme activity.\n CYP2C19<\/jats:italic>\n mice were hyperdopaminergic; however, the motoric impairment was not ameliorated by dopamine receptor antagonists, and there was no alteration in the number of midbrain dopaminergic neurons in\n CYP2C19<\/jats:italic>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Humanised\n CYP2C19<\/jats:italic>\n transgenic mice exhibit altered gait and functional motoric impairments; this phenotype is likely caused by an aberrant cerebellar development.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/nan.12867","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T23:32:25Z","timestamp":1671492745000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The humanised\n CYP2C19<\/i>\n transgenic mouse exhibits cerebellar atrophy and movement impairment reminiscent of ataxia"],"prefix":"10.1111","volume":"49","author":[{"given":"Filip","family":"Milosavljevi\u0107","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Pharmacy University of Belgrade Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irene","family":"Brusini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Health Systems KTH Royal Institute of Technology Huddinge Sweden"},{"name":"Department of Neurobiology, Care Sciences and Society Karolinska Institute Huddinge Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Atanasov","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Pharmacy University of Belgrade Belgrade 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University of Belgrade Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering and Health Systems KTH Royal Institute of Technology Huddinge Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Damberg","sequence":"additional","affiliation":[{"name":"Karolinska Experimental Research and Imaging Center Karolinska University Hospital Solna Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vesna","family":"Pe\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Pharmacy University of Belgrade Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel F.","family":"Tyndale","sequence":"additional","affiliation":[{"name":"Campbell Family Mental Health Research Institute Centre for Addiction and Mental Health Toronto Ontario 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