{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:28:27Z","timestamp":1790713707202,"version":"4.1.0"},"reference-count":46,"publisher":"National Academy of Sciences","issue":"23","license":[{"start":{"date-parts":[[2018,11,16]],"date-time":"2018-11-16T00:00:00Z","timestamp":1542326400000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/100000025","name":"HHS | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH102711"],"award-info":[{"award-number":["MH102711"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,6,5]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Rett syndrome (RTT) is a severe neurological disease affecting girls in their early childhood. The underlying cause of most RTT cases is mutations in the gene methyl-CpG-binding protein 2 (\n                    <jats:italic>MECP2<\/jats:italic>\n                    ). How the loss of MeCP2 function in the brain due to these mutations causes such severe neurological symptoms remains a mystery. Here, we show widespread aberrations in gene expression and anomalous patterns of alternative splicing, specifically when neurons of RTT mice are stimulated. Furthermore, these aberrations occur in conjunction with higher seizure susceptibility in response to neuronal stimulation in these RTT mice. Our findings suggest that MeCP2 is required for adjusting the robust changes in gene transcription and for proper regulation of alternative splicing during neuronal stimulation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1722546115","type":"journal-article","created":{"date-parts":[[2018,5,16]],"date-time":"2018-05-16T18:33:40Z","timestamp":1526495620000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":52,"title":["Activity-dependent aberrations in gene expression and alternative splicing in a mouse model of Rett syndrome"],"prefix":"10.1073","volume":"115","author":[{"given":"Sivan","family":"Osenberg","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel","family":"Karten","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Texas A&amp;M University, College Station, TX 77843;"},{"name":"TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering, Texas A&amp;M University, College Station, TX 77843;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun","family":"Charkowick","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christy A.","family":"Felice","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Kritzer","sequence":"additional","affiliation":[{"name":"Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minh Vu Chuong","family":"Nguyen","sequence":"additional","affiliation":[{"name":"GREPI-UGA EA7408, Universit\u00e9 Grenoble Alpes, 38400 Saint-Martin-d\u2019H\u00e8res, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Texas A&amp;M University, College Station, TX 77843;"},{"name":"TEES-AgriLife Center for Bioinformatics and Genomic Systems Engineering, Texas A&amp;M University, College Station, TX 77843;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurit","family":"Ballas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Cell Biology, Stony Brook University, Stony Brook, NY 11794;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2018,5,16]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.neuron.2007.10.001","article-title":"The story of Rett syndrome: From clinic to neurobiology","volume":"56","author":"Chahrour M","year":"2007","unstructured":"M Chahrour, HY Zoghbi, The story of Rett syndrome: From clinic to neurobiology. Neuron 56, 422\u2013437 (2007).","journal-title":"Neuron"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2","volume":"23","author":"Amir RE","year":"1999","unstructured":"RE Amir, , Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 23, 185\u2013188 (1999).","journal-title":"Nat Genet"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"15536","DOI":"10.1073\/pnas.242566899","article-title":"Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain","volume":"99","author":"Tudor M","year":"2002","unstructured":"M Tudor, S Akbarian, RZ Chen, R Jaenisch, Transcriptional profiling of a mouse model for Rett syndrome reveals subtle transcriptional changes in the brain. 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Mol Cell 37, 457\u2013468 (2010).","journal-title":"Mol Cell"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"2894","DOI":"10.1128\/MCB.06728-11","article-title":"Phosphorylation of distinct sites in MeCP2 modifies cofactor associations and the dynamics of transcriptional regulation","volume":"32","author":"Gonzales ML","year":"2012","unstructured":"ML Gonzales, S Adams, KW Dunaway, JM LaSalle, Phosphorylation of distinct sites in MeCP2 modifies cofactor associations and the dynamics of transcriptional regulation. 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