{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:38:08Z","timestamp":1790469488935,"version":"4.1.0"},"reference-count":56,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T00:00:00Z","timestamp":1473292800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns4:p>\n                    Rett syndrome\u00a0(RTT) is a neurodevelopmental disorder caused by mutation in the X-linked\n                    <ns4:italic>MECP2<\/ns4:italic>\n                    gene, encoding methyl-CpG-binding protein 2. We have created a mouse model (\n                    <ns4:italic>Mecp2<\/ns4:italic>\n                    A140V \u201cknock-in\u201d mutant) expressing the recurrent human\n                    <ns4:italic>MECP2<\/ns4:italic>\n                    A140V mutation linked to an X-linked mental retardation\/Rett syndrome phenotype. Morphological analyses focused on quantifying soma and nucleus size were performed on primary hippocampus and cerebellum granule neuron (CGN) cultures from mutant (\n                    <ns4:italic>Mecp2<\/ns4:italic>\n                    <ns4:sup>A140V\/y<\/ns4:sup>\n                    ) and wild type (\n                    <ns4:italic>Mecp2<\/ns4:italic>\n                    <ns4:sup>+\/y<\/ns4:sup>\n                    ) male mice. Cultured hippocampus and cerebellar granule neurons from mutant animals were significantly smaller than neurons from wild type animals. We also examined soma size in hippocampus neurons from individual female transgenic mice that express both a mutant\u00a0 (maternal allele) and a wild type\n                    <ns4:italic>Mecp2<\/ns4:italic>\n                    gene linked to an eGFP transgene (paternal allele). In cultures from such doubly heterozygous female mice, the size of neurons expressing the mutant (A140V) allele also showed a significant reduction compared to neurons expressing wild type MeCP2, supporting a cell-autonomous role for MeCP2 in neuronal development. IGF-1 (insulin growth factor-1) treatment of neuronal cells from\n                    <ns4:italic>Mecp2<\/ns4:italic>\n                    mutant mice rescued the soma size phenotype. We also found that\n                    <ns4:italic>Mecp2<\/ns4:italic>\n                    <ns4:italic>\u00a0<\/ns4:italic>\n                    mutation leads to down-regulation of the mTOR signaling pathway, known to be involved in neuronal size regulation. Our results suggest that i) reduced neuronal size is an important\n                    <ns4:italic>in vitro<\/ns4:italic>\n                    cellular phenotype of\n                    <ns4:italic>Mecp2<\/ns4:italic>\n                    mutation in mice, and ii) MeCP2 might play a critical role in the maintenance of neuronal structure by modulation of the mTOR pathway. The definition of a quantifiable cellular phenotype supports using neuronal size as a biomarker in the development of a high-throughput,\n                    <ns4:italic>in vitro<\/ns4:italic>\n                    assay to screen for compounds that rescue small neuronal phenotype (\u201cphenotypic assay\u201d).\n                  <\/ns4:p>","DOI":"10.12688\/f1000research.8156.1","type":"journal-article","created":{"date-parts":[[2016,9,8]],"date-time":"2016-09-08T05:20:22Z","timestamp":1473312022000},"page":"2269","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["Reduced neuronal size and mTOR pathway activity in the Mecp2 A140V Rett syndrome mouse model"],"prefix":"10.12688","volume":"5","author":[{"given":"Sampathkumar","family":"Rangasamy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Olfers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Gerald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Hilbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Svejda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinodh","family":"Narayanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2016,9,8]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"185-8","DOI":"10.1038\/13810","article-title":"Rett 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Amir","year":"2000","journal-title":"Ann Neurol."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"102-7","DOI":"10.1002\/ajmg.b.10070","article-title":"Study of MECP2 gene in Rett syndrome variants and autistic girls.","volume":"119B","author":"M Zappella","year":"2003","journal-title":"Am J Med Genet B Neuropsychiatr Genet."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"91-4","DOI":"10.1111\/dmcn.12334","article-title":"Adolescent onset cognitive regression and neuropsychiatric symptoms associated with the A140V MECP2 mutation.","volume":"56","author":"S Venkateswaran","year":"2014","journal-title":"Dev Med Child Neurol."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"1034-7","DOI":"10.1086\/339553","article-title":"A mutation hot spot for nonspecific X-linked mental retardation in the MECP2 gene causes the PPM-X syndrome.","volume":"70","author":"S Klauck","year":"2002","journal-title":"Am J Hum Genet."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"941-6","DOI":"10.1093\/hmg\/10.9.941","article-title":"MECP2 is highly mutated in X-linked mental retardation.","volume":"10","author":"P Couvert","year":"2001","journal-title":"Hum Mol Genet."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"285-8","DOI":"10.1016\/S0014-5793(00)01994-3","article-title":"MECP2 mutation in male patients with non-specific X-linked mental retardation.","volume":"481","author":"A Orrico","year":"2000","journal-title":"FEBS Lett."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"2709-14","DOI":"10.1073\/pnas.0608056104","article-title":"Interaction between chromatin proteins MECP2 and ATRX is disrupted by mutations that cause inherited mental retardation.","volume":"104","author":"X Nan","year":"2007","journal-title":"Proc Natl Acad Sci U S A."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/1471-2202-11-19","article-title":"Abnormalities of cell packing density and dendritic complexity in the MeCP2 A140V mouse model of Rett syndrome\/X-linked mental retardation.","volume":"11","author":"G Jentarra","year":"2010","journal-title":"BMC Neurosci."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"72-6","DOI":"10.1002\/mrdd.10027","article-title":"Neuropathology of Rett syndrome.","volume":"8","author":"D Armstrong","year":"2002","journal-title":"Ment Retard Dev Disabil Res Rev."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"105-8","DOI":"10.1055\/s-2007-979737","article-title":"Microscopic observations of the brain in Rett syndrome.","volume":"26","author":"M Bauman","year":"1995","journal-title":"Neuropediatrics."},{"key":"ref-14","doi-asserted-by":"publisher","first-page":"309-16","DOI":"10.1016\/j.pedneo.2011.08.002","article-title":"Rett syndrome: from bed to bench.","volume":"52","author":"S Weng","year":"2011","journal-title":"Pediatr Neonatol."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"383-91","DOI":"10.1016\/S0301-0082(96)00059-7","article-title":"Rett syndrome: neurobiological changes underlying specific symptoms.","volume":"51","author":"G Wenk","year":"1997","journal-title":"Prog Neurobiol."},{"key":"ref-16","doi-asserted-by":"publisher","first-page":"1581-6","DOI":"10.1212\/WNL.45.8.1581","article-title":"Pervasive neuroanatomic abnormalities of the brain in three cases of Rett\u2019s syndrome.","volume":"45","author":"M Bauman","year":"1995","journal-title":"Neurology."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"1013-7","DOI":"10.1097\/00005072-199811000-00003","article-title":"Decreased dendritic branching in frontal, motor and limbic cortex in Rett syndrome compared with trisomy 21.","volume":"57","author":"D Armstrong","year":"1998","journal-title":"J Neuropathol Exp 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Neurosci."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"907-21","DOI":"10.1016\/j.neuroscience.2007.02.009","article-title":"Behavioral and anatomical abnormalities in Mecp2 mutant mice: a model for Rett syndrome.","volume":"146","author":"N Stearns","year":"2007","journal-title":"Neuroscience."},{"key":"ref-22","doi-asserted-by":"publisher","first-page":"77-89","DOI":"10.1016\/j.nbd.2007.04.005","article-title":"Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons.","volume":"27","author":"R Smrt","year":"2007","journal-title":"Neurobiol Dis."},{"key":"ref-23","doi-asserted-by":"publisher","first-page":"3-12","DOI":"10.1016\/j.nbd.2013.04.020","article-title":"Neuronal morphology in MeCP2 mouse models is intrinsically variable and depends on age, cell type, and Mecp2 mutation.","volume":"58","author":"I Wang","year":"2013","journal-title":"Neurobiol 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Neurosci."},{"key":"ref-41","doi-asserted-by":"publisher","first-page":"12187-95","DOI":"10.1523\/JNEUROSCI.3156-09.2009","article-title":"Pathophysiology of locus ceruleus neurons in a mouse model of Rett syndrome.","volume":"29","author":"P Taneja","year":"2009","journal-title":"J Neurosci."},{"key":"ref-42","doi-asserted-by":"publisher","first-page":"145","DOI":"10.3389\/fncel.2015.00145","article-title":"Genotype-specific effects of Mecp2 loss-of-function on morphology of Layer V pyramidal neurons in heterozygous female Rett syndrome model mice.","volume":"9","author":"L Rietveld","year":"2015","journal-title":"Front Cell Neurosci."},{"key":"ref-43","doi-asserted-by":"publisher","first-page":"1931-6","DOI":"10.1073\/pnas.0610593104","article-title":"Partial rescue of MeCP2 deficiency by postnatal activation of MeCP2.","volume":"104","author":"E Giacometti","year":"2007","journal-title":"Proc Natl Acad Sci 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Lioy","year":"2011","journal-title":"Nature."},{"key":"ref-50","doi-asserted-by":"publisher","first-page":"4596-601","DOI":"10.1073\/pnas.1311141111","article-title":"Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome.","volume":"111","author":"O Khwaja","year":"2014","journal-title":"Proc Natl Acad Sci USA."},{"key":"ref-51","doi-asserted-by":"publisher","first-page":"1821-7","DOI":"10.1158\/0008-5472.CAN-08-3014","article-title":"TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2.","volume":"69","author":"J Copp","year":"2009","journal-title":"Cancer Res."},{"key":"ref-52","doi-asserted-by":"publisher","first-page":"1472-87","DOI":"10.1101\/gad.995802","article-title":"Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1\/eIF4E.","volume":"16","author":"D Fingar","year":"2002","journal-title":"Genes Dev."},{"key":"ref-53","doi-asserted-by":"publisher","first-page":"24361-75","DOI":"10.18632\/oncotarget.4458","article-title":"eIF3 controls cell size independently of S6K1-activity.","volume":"6","author":"K Schipany","year":"2015","journal-title":"Oncotarget."},{"key":"ref-54","doi-asserted-by":"publisher","first-page":"299-301","DOI":"10.1038\/clpt.2012.236","article-title":"Phenotypic vs. target-based drug discovery for first-in-class medicines.","volume":"93","author":"D Swinney","year":"2013","journal-title":"Clin Pharmacol Ther."},{"key":"ref-55","doi-asserted-by":"publisher","first-page":"507-19","DOI":"10.1038\/nrd3480","article-title":"How were new medicines discovered?","volume":"10","author":"D Swinney","year":"2011","journal-title":"Nat Rev Drug Discov."},{"key":"ref-56","doi-asserted-by":"publisher","DOI":"10.5256\/f1000research.8156.d134352","article-title":"Dataset 1 in: Reduced neuronal size and mTOR pathway activity in the 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Mochida, Division of Genetics and Genomics, Department of Medicine, Boston Children's Hospital, Boston, MA, USA, 19 Oct 2016, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/5-2269\/v1#referee-response-16241","order":3,"name":"referee-response-16241","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"Supported by intramural funds from the Barrow Neurological Foundation and the Center for Rare Childhood Disorders at TGen to Vinodh Narayanan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Data associated with the article are available under the terms of the Creative Commons Zero \"No rights reserved\" data waiver (CC0 1.0 Public domain dedication).","order":0,"name":"copyright-info","label":"Copyright"}]}}