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In this work, we generated novel transgenic mouse models expressing low levels of wild-type and mutant human FUS, both of which recapitulate aspects of the human diseases. We found a profound difference in the underlying mechanisms by which missense mutation and wild-type overexpression cause disease. Overexpression of wild-type FUS protein alters its nuclear function at the level of gene expression. In contrast, missense mutation disrupts activity-dependent synaptic homeostasis to gain a toxic function at dendritic spines.<\/jats:p>","DOI":"10.1073\/pnas.1406162111","type":"journal-article","created":{"date-parts":[[2014,10,17]],"date-time":"2014-10-17T08:20:08Z","timestamp":1413534008000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":138,"title":["Activity-dependent FUS dysregulation disrupts synaptic homeostasis"],"prefix":"10.1073","volume":"111","author":[{"given":"Chantelle F.","family":"Sephton","sequence":"first","affiliation":[{"name":"Departments of aNeuroscience and"},{"name":"Institut Universitaire en Sant\u00e9 Mentale de Qu\u00e9bec, Department of Psychiatry and Neuroscience, Universit\u00e9 Laval, Quebec City, QC, Canada G1J 2G3;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy A.","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neuropathology and 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