Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition

article Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition published yes Elena Deliu author 37A40D7E-F248-11E8-B48F-1D18A9856A870000-0002-7370-5293 Niccoló Arecco author Jasmin Morandell author 4739D480-F248-11E8-B48F-1D18A9856A87 Christoph Dotter author 4C66542E-F248-11E8-B48F-1D18A9856A870000-0002-9033-9096 Ximena Contreras author 475990FE-F248-11E8-B48F-1D18A9856A87 Charles Girardot author Eva Käsper author Alena Kozlova author C50A9596-02D0-11E9-976E-E38CFE5CBC1D Kasumi Kishi author 3065DFC4-F248-11E8-B48F-1D18A9856A870000-0001-6060-4795 Ilaria Chiaradia author B6467F20-02D0-11E9-BDA5-E960C241894A0000-0002-9529-4464 Kyung Noh author Gaia Novarino author 3E57A680-F248-11E8-B48F-1D18A9856A870000-0002-7673-7178 GaNo department EdHa department Probing development and reversibility of autism spectrum disorders project SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder. https://research-explorer.ista.ac.at/download/3/6255/2017_NatureNeuroscience_Deliu.pdf application/pdfno Nature Publishing Group2018 eng Nature Neuroscience 00045132470001010.1038/s41593-018-0266-2 21121717 - 1727 https://research-explorer.ista.ac.at/record/6074 https://research-explorer.ista.ac.at/record/12364 https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/ Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 21(12), 1717–1727. E. Deliu et al., “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition,” Nature Neuroscience, vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018. Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience, vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:<a href="https://doi.org/10.1038/s41593-018-0266-2">10.1038/s41593-018-0266-2</a>. E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot, E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience 21 (2018) 1717–1727. Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 2018;21(12):1717-1727. doi:<a href="https://doi.org/10.1038/s41593-018-0266-2">10.1038/s41593-018-0266-2</a> Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot, C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. Nature Publishing Group. <a href="https://doi.org/10.1038/s41593-018-0266-2">https://doi.org/10.1038/s41593-018-0266-2</a> Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience. Nature Publishing Group, 2018. <a href="https://doi.org/10.1038/s41593-018-0266-2">https://doi.org/10.1038/s41593-018-0266-2</a>. 32018-12-11T11:44:05Z2026-04-20T22:30:33Z