{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T18:07:08Z","timestamp":1785866828940,"version":"3.56.0"},"reference-count":57,"publisher":"The Company of Biologists","issue":"7","license":[{"start":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T00:00:00Z","timestamp":1720569600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Collaborative Center for X-linked Dystonia-Parkinsonism","award":["239295"],"award-info":[{"award-number":["239295"]}]},{"name":"Collaborative Center for X-linked Dystonia-Parkinsonism","award":["F22-01451"],"award-info":[{"award-number":["F22-01451"]}]},{"DOI":"10.13039\/501100005247","name":"University of British Columbia","doi-asserted-by":"crossref","award":["PM007960"],"award-info":[{"award-number":["PM007960"]}],"id":[{"id":"10.13039\/501100005247","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The TATA box-binding protein-associated factor 1 (TAF1) is a ubiquitously expressed protein and the largest subunit of the basal transcription factor TFIID, which plays a key role in initiation of RNA polymerase II-dependent transcription. TAF1 missense variants in human males cause X-linked intellectual disability, a neurodevelopmental disorder, and TAF1 is dysregulated in X-linked dystonia\u2013parkinsonism, a neurodegenerative disorder. However, this field has lacked a genetic mouse model of TAF1 disease to explore its mechanism in mammals and treatments. Here, we generated and validated a conditional cre-lox allele and the first ubiquitous Taf1 knockout mouse. We discovered that Taf1 deletion in male mice was embryonically lethal, which may explain why no null variants have been identified in humans. In the brains of Taf1 heterozygous female mice, no differences were found in gross structure, overall expression and protein localisation, suggesting extreme skewed X inactivation towards the non-mutant chromosome. Nevertheless, these female mice exhibited a significant increase in weight, weight with age, and reduced movement, suggesting that a small subset of neurons was negatively impacted by Taf1 loss. Finally, this new mouse model may be a future platform for the development of TAF1 disease therapeutics.<\/jats:p>","DOI":"10.1242\/dmm.050741","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T12:57:02Z","timestamp":1716901022000},"source":"Crossref","is-referenced-by-count":7,"title":["<i>Taf1<\/i> knockout is lethal in embryonic male mice and heterozygous females show weight and movement disorders"],"prefix":"10.1242","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4806-6140","authenticated-orcid":false,"given":"Elisa M.","family":"Crombie","sequence":"first","affiliation":[{"name":"UCL Institute of Neurology, University College London 1 Department of Neuromuscular Diseases , , London WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6532-0695","authenticated-orcid":false,"given":"Andrea J.","family":"Korecki","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics at BC Children's Hospital, University of British Columbia 2 , Vancouver, BC V5Z 4H4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2517-687X","authenticated-orcid":false,"given":"Karen","family":"Cleverley","sequence":"additional","affiliation":[{"name":"UCL Institute of Neurology, University College London 1 Department of Neuromuscular Diseases , , London WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9677-7962","authenticated-orcid":false,"given":"Bethany A.","family":"Adair","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics at BC Children's Hospital, University of British Columbia 2 , Vancouver, BC V5Z 4H4 , Canada"},{"name":"University of British Columbia 3 Department of Medical Genetics , , Vancouver V6T 1Z3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8859-9481","authenticated-orcid":false,"given":"Thomas J.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"MRC Harwell Institute 4 , Harwell Campus, Oxfordshire OX11 0RD , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9447-1174","authenticated-orcid":false,"given":"Weaverly Colleen","family":"Lee","sequence":"additional","affiliation":[{"name":"UCL Institute of Neurology, University College London 1 Department of Neuromuscular Diseases , , London WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6292-0724","authenticated-orcid":false,"given":"Tess C.","family":"Lengyell","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics at BC Children's Hospital, University of British Columbia 2 , Vancouver, BC V5Z 4H4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8624-6251","authenticated-orcid":false,"given":"Cheryl","family":"Maduro","sequence":"additional","affiliation":[{"name":"UCL Institute of Neurology, University College London 1 Department of Neuromuscular Diseases , , London WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5242-2649","authenticated-orcid":false,"given":"Victor","family":"Mo","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics at BC Children's Hospital, University of British Columbia 2 , Vancouver, BC V5Z 4H4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6131-5539","authenticated-orcid":false,"given":"Liam M.","family":"Slade","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics at BC Children's Hospital, University of British Columbia 2 , Vancouver, BC V5Z 4H4 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5022-5433","authenticated-orcid":false,"given":"Ines","family":"Zouhair","sequence":"additional","affiliation":[{"name":"UCL Institute of Neurology, University College London 1 Department of Neuromuscular Diseases , , London WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2850-9936","authenticated-orcid":false,"given":"Elizabeth M. C.","family":"Fisher","sequence":"additional","affiliation":[{"name":"UCL Institute of Neurology, University College London 1 Department of Neuromuscular Diseases , , London WC1N 3BG , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0654-4303","authenticated-orcid":false,"given":"Elizabeth M.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Centre for Molecular Medicine and Therapeutics at BC Children's Hospital, University of British Columbia 2 , Vancouver, BC V5Z 4H4 , Canada"},{"name":"University of British Columbia 3 Department of Medical Genetics , , Vancouver V6T 1Z3 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,7,10]]},"reference":[{"key":"2024071007391350600_DMM050741C1","doi-asserted-by":"publisher","first-page":"6263","DOI":"10.1523\/JNEUROSCI.4757-04.2005","article-title":"Pathological aggression in \u201cfierce\u201d mice corrected by human nuclear receptor 2E1","volume":"25","author":"Abrahams","year":"2005","journal-title":"J. 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