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There is evidence to suggest that the splicing factor SRSF6 is involved in the mechanism that underlies this aberrant splicing event. Therefore, we set out to test this hypothesis, by manipulating SRSF6 levels in Huntington\u2019s disease models in which an expanded CAG repeat had been knocked in to the endogenous<jats:italic>Htt<\/jats:italic>gene. We began by generating mice that were knocked out for<jats:italic>Srsf6<\/jats:italic>, and demonstrated that reduction of SRSF6 to 50% of wild type levels had no effect on incomplete splicing in zQ175 knockin mice. We found that nullizygosity for<jats:italic>Srsf6<\/jats:italic>was embryonic lethal, and therefore, to decrease SRSF6 levels further, we established mouse embryonic fibroblasts (MEFs) from wild type, zQ175, and zQ175::<jats:italic>Srsf6<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>mice and transfected them with an<jats:italic>Srsf6<\/jats:italic>siRNA. The incomplete splicing of<jats:italic>Htt<\/jats:italic>was recapitulated in the MEFs and we demonstrated that ablation of SRSF6 did not modulate the levels of the<jats:italic>Httexon1<\/jats:italic>transcript. We conclude that SRSF6 is not required for the incomplete splicing of<jats:italic>HTT<\/jats:italic>in Huntington\u2019s disease.<\/jats:p>","DOI":"10.1038\/s41598-020-71111-w","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T10:07:20Z","timestamp":1597918040000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Silencing Srsf6 does not modulate incomplete splicing of the huntingtin gene in Huntington\u2019s disease models"],"prefix":"10.1038","volume":"10","author":[{"given":"Michael A.","family":"Mason","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casandra","family":"Gomez-Paredes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirupa","family":"Sathasivam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Neueder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini-Smaragdi","family":"Papadopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian P.","family":"Bates","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"71111_CR1","doi-asserted-by":"publisher","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","volume":"1","author":"GP Bates","year":"2015","unstructured":"Bates, G. 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