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Taf1 knockout is lethal in embryonic male mice and heterozygous females show weight and movement disorders.
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- Additional Information
- Source:
Publisher: Company of Biologists Ltd Country of Publication: England NLM ID: 101483332 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1754-8411 (Electronic) Linking ISSN: 17548403 NLM ISO Abbreviation: Dis Model Mech Subsets: MEDLINE
- Publication Information:
Original Publication: Cambridge : Company of Biologists Ltd., c2008-
- Subject Terms:
- Abstract:
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-parkinsonism, 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.
Competing Interests: Competing interests The authors declare no competing or financial interests.
(© 2024. Published by The Company of Biologists Ltd.)
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- Grant Information:
#239295 Collaborative Center for X linked Dystonia-Parkinsonism (CCXDP); Faculty of Medicine University of British Columbia; 239295 Collaborative Center for X-linked Dystonia-Parkinsonism; PM007960 University of British Columbia
- Contributed Indexing:
Keywords: Genetic mouse model; Male lethality; TATA box-binding protein-associated factor 1; Transcription initiation complex; X inactivation; X-linked dystonia–parkinsonism; X-linked intellectual disability
- Accession Number:
0 (TATA-Binding Protein Associated Factors)
0 (Transcription Factor TFIID)
EC 2.7.11.1 (TATA-binding protein associated factor 250 kDa)
EC 2.3.1.48 (Histone Acetyltransferases)
- Publication Date:
Date Created: 20240528 Date Completed: 20240710 Latest Revision: 20240724
- Publication Date:
20240725
- Accession Number:
PMC11261634
- Accession Number:
10.1242/dmm.050741
- Accession Number:
38804708
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