{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T23:34:38Z","timestamp":1792712078806,"version":"4.5.0"},"reference-count":71,"publisher":"Society for Neuroscience","issue":"19","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":212,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2020,5,6]]},"abstract":"<jats:p>\n                    <jats:italic>MECP2<\/jats:italic>\n                    gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where\n                    <jats:italic>MECP2<\/jats:italic>\n                    mutation affects the monkey brain and whether\/how it relates to autism pathology remain unknown. Here we report a combination of gene\u2013circuit\u2013behavior analyses including\n                    <jats:italic>MECP2<\/jats:italic>\n                    coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5\n                    <jats:italic>MECP2<\/jats:italic>\n                    overexpressed monkeys (\n                    <jats:italic>Macaca fascicularis<\/jats:italic>\n                    ; 3 females) and 20 wild-type monkeys (\n                    <jats:italic>Macaca fascicularis<\/jats:italic>\n                    ; 11 females). Whole-genome expression analysis revealed\n                    <jats:italic>MECP2<\/jats:italic>\n                    coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced \u03b2-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile,\n                    <jats:italic>MECP2<\/jats:italic>\n                    -induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene\u2013circuit\u2013behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as\n                    <jats:italic>MECP2<\/jats:italic>\n                    . However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of\n                    <jats:italic>MECP2<\/jats:italic>\n                    overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to\n                    <jats:italic>MECP2<\/jats:italic>\n                    and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.2727-19.2020","type":"journal-article","created":{"date-parts":[[2020,5,6]],"date-time":"2020-05-06T17:45:35Z","timestamp":1588787135000},"page":"3799-3814","source":"Crossref","is-referenced-by-count":36,"title":["<i>MECP2<\/i>\n                    Duplication Causes Aberrant GABA Pathways, Circuits and Behaviors in Transgenic Monkeys: Neural Mappings to Patients with Autism"],"prefix":"10.1523","volume":"40","author":[{"given":"Dan-Chao","family":"Cai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5863-9785","authenticated-orcid":false,"given":"Zhiwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Bo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengyao","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaowen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4244-5636","authenticated-orcid":false,"given":"Kristina","family":"Zeljic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9554-3715","authenticated-orcid":false,"given":"Xiaoyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yafeng","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingwei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Cang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Zhong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilong","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjin","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1912-6992","authenticated-orcid":false,"given":"Zheng","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7138-8581","authenticated-orcid":false,"given":"Zheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2020,4,8]]},"reference":[{"key":"2023041803412137000_40.19.3799.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.12.005"},{"key":"2023041803412137000_40.19.3799.2","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"2023041803412137000_40.19.3799.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2008.07.014"},{"key":"2023041803412137000_40.19.3799.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.03.002"},{"key":"2023041803412137000_40.19.3799.5","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy111"},{"key":"2023041803412137000_40.19.3799.6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0808281"},{"key":"2023041803412137000_40.19.3799.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.1172377"},{"key":"2023041803412137000_40.19.3799.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature09582"},{"key":"2023041803412137000_40.19.3799.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcn.2014.12.005"},{"key":"2023041803412137000_40.19.3799.10","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.161"},{"key":"2023041803412137000_40.19.3799.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2003.10.009"},{"key":"2023041803412137000_40.19.3799.12","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2013.78"},{"key":"2023041803412137000_40.19.3799.13","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4246"},{"key":"2023041803412137000_40.19.3799.14","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00050-2"},{"key":"2023041803412137000_40.19.3799.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1115365109"},{"key":"2023041803412137000_40.19.3799.16","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00569-X"},{"key":"2023041803412137000_40.19.3799.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091322"},{"key":"2023041803412137000_40.19.3799.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2008.11.006"},{"key":"2023041803412137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