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Such models exist but mostly comprise non\u2010human or non\u2010neuronal cells that may not recapitulate the correct biochemical milieu involved in pathology. We have developed a new human neuronal cell model of HD, using neural stem cells (ReNcell VM NSCs) stably transduced to express exon 1 huntingtin (HTT) fragments with variable length polyglutamine (polyQ) tracts. Using a system with matched expression levels of exon 1 HTT fragments, we investigated the effect of increasing polyQ repeat length on HTT inclusion formation, location, neuronal survival, and mitochondrial function with a view to creating an in vitro screening platform for therapeutic screening. We found that expression of exon 1 HTT fragments with longer polyQ tracts led to the formation of intra\u2010nuclear inclusions in a polyQ length\u2010dependent manner during neurogenesis. There was no overt effect on neuronal viability, but defects of mitochondrial function were found in the pathogenic lines. Thus, we have a human neuronal cell model of HD that may recapitulate some of the earliest stages of HD pathogenesis, namely inclusion formation and mitochondrial dysfunction.<\/jats:p>","DOI":"10.1096\/fj.201902277rr","type":"journal-article","created":{"date-parts":[[2020,4,23]],"date-time":"2020-04-23T23:41:08Z","timestamp":1587685268000},"page":"8139-8154","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Expression of mutant exon 1 huntingtin fragments in human neural stem cells and neurons causes inclusion formation and mitochondrial dysfunction"],"prefix":"10.1096","volume":"34","author":[{"given":"Rhia","family":"Ghosh","sequence":"first","affiliation":[{"name":"Huntington's Disease Centre Department of Neurodegenerative Disease UCL Queen Square Institute of Neurology University College London London 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