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Although sensory neuron degeneration in the peripheral nervous system during the early postnatal stage is a well\u2010recognised phenotype in <jats:italic>dt<\/jats:italic>, the histological characteristics and neuronal circuits in the central nervous system responsible for motor symptoms remain unclear. To analyse the causative neuronal networks and roles of <jats:italic>Dst<\/jats:italic> isoforms, we generated novel multipurpose <jats:italic>Dst<\/jats:italic> gene trap mice, in which actin\u2010binding domain\u2010containing isoforms are disrupted. Homozygous mice showed typical <jats:italic>dt<\/jats:italic> phenotypes with sensory degeneration and progressive motor symptoms. The gene trap allele (<jats:italic>Dst<\/jats:italic><jats:sup><jats:italic>Gt<\/jats:italic><\/jats:sup>) encodes a mutant Dystonin\u2010LacZ fusion protein, which is detectable by X\u2010gal (5\u2010bromo\u20104\u2010chloro\u20103\u2010indolyl\u2010\u03b2\u2010D\u2010galactoside) staining. We observed wide expression of the actin\u2010binding domain\u2010containing <jats:italic>Dystonin<\/jats:italic> isoforms in the central nervous system (<jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>) and peripheral nervous system. This raised the possibility that not only secondary neuronal defects in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> subsequent to peripheral sensory degeneration but also cell\u2010autonomous defects in the <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content> contribute to the motor symptoms. Expression analysis of immediate early genes revealed decreased neuronal activity in the cerebellar\u2010thalamo\u2010striatal pathway in the homozygous brain, implying the involvement of this pathway in the <jats:italic>dt<\/jats:italic> phenotype. These novel <jats:italic>Dst<\/jats:italic><jats:sup><jats:italic>Gt<\/jats:italic><\/jats:sup> mice showed that a loss\u2010of\u2010function mutation in the actin\u2010binding domain\u2010containing <jats:italic>Dystonin<\/jats:italic> isoforms led to typical <jats:italic>dt<\/jats:italic> phenotypes. Furthermore, this novel multipurpose <jats:italic>Dst<\/jats:italic><jats:sup><jats:italic>Gt<\/jats:italic><\/jats:sup> allele offers a unique tool for analysing the causative neuronal networks involved in the <jats:italic>dt<\/jats:italic> phenotype.<\/jats:p>","DOI":"10.1111\/ejn.12711","type":"journal-article","created":{"date-parts":[[2014,9,6]],"date-time":"2014-09-06T07:51:24Z","timestamp":1409989884000},"page":"3458-3471","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Disruption of actin\u2010binding domain\u2010containing <scp>D<\/scp>ystonin protein causes <i>dystonia musculorum<\/i> in mice"],"prefix":"10.1111","volume":"40","author":[{"given":"Masao","family":"Horie","sequence":"first","affiliation":[{"name":"Division of Neurobiology and Anatomy Graduate School of Medical and Dental Sciences Niigata University Asahimachi Chuo\u2010ku Niigata 951\u20108510 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