{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:22:14Z","timestamp":1790634134627,"version":"4.1.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Creatine transporter deficiency (CTD), a leading cause of intellectual disability is a result of the mutation in the gene encoding the creatine transporter SLC6A8, which prevents creatine uptake into the brain, causing mental retardation, expressive speech and language delay, autistic-like behavior and epilepsy. Preclinical <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> data indicate that dodecyl creatine ester (DCE) which increases the creatine brain content, might be a therapeutic option for CTD patients. To gain a better understanding of the pathophysiology and DCE treatment efficacy in CTD, this study focuses on the identification of biomarkers related to cognitive improvement in a Slc6a8 knockout mouse model (Slc6a8\u2212\/y) engineered to mimic the clinical features of CTD patients which have low brain creatine content. Shotgun proteomics analysis of 4,035 proteins in four different brain regions; the cerebellum, cortex, hippocampus (associated with cognitive functions) and brain stem, and muscle as a control, was performed in 24 mice. Comparison of the protein abundance in the four brain regions between DCE-treated intranasally Slc6a8\u2212\/y mice and wild type and DCE-treated Slc6a8\u2212\/y and vehicle group identified 14 biomarkers, shedding light on the mechanism of action of DCE. Integrative bioinformatics and statistical modeling identified key proteins in CTD, including KIF1A and PLCB1. The abundance of these proteins in the four brain regions was significantly correlated with both the object recognition and the Y-maze tests. Our findings suggest a major role for PLCB1, KIF1A, and associated molecules in the pathogenesis of CTD.<\/jats:p>","DOI":"10.3389\/fnmol.2023.1118707","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T11:30:28Z","timestamp":1679657428000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":11,"title":["Dodecyl creatine ester improves cognitive function and identifies key protein drivers including KIF1A and PLCB1 in a mouse model of creatine transporter deficiency"],"prefix":"10.3389","volume":"16","author":[{"given":"Alo\u00efse","family":"Mabondzo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Harati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Broca-Brisson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-C\u00e9cile","family":"Guyot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narciso","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Cacciante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Putignano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Baroncelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Skelton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Saab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Martini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Benech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Joudinaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Charles","family":"Gaillard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Armengaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rifat","family":"Hamoudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1152\/physrev.00017.2008","article-title":"Transcription factors in long-term memory and synaptic plasticity","volume":"89","author":"Alberini","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"5171","DOI":"10.1038\/s41467-020-18956-x","article-title":"Synapse type-specific proteomic dissection identifies IgSF8 as a hippocampal CA3 microcircuit organizer","volume":"11","author":"Apostolo","year":"2020","journal-title":"Nat. Commun."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1016\/j.biopsych.2004.01.009","article-title":"Association of neural cell adhesion molecule 1 gene polymorphisms with bipolar affective disorder in Japanese individuals","volume":"55","author":"Arai","year":"2004","journal-title":"Biol. Psychiatry"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1097\/YPG.0b013e328012d850","article-title":"NCAM1 association study of bipolar disorder and schizophrenia: polymorphisms and alternatively spliced isoforms lead to similarities and differences","volume":"17","author":"Atz","year":"2007","journal-title":"Psychiatr. Genet."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1002\/cne.903180207","article-title":"Efferent cortical connections of multimodal cortex of the superior temporal sulcus in the rhesus monkey","volume":"318","author":"Barnes","year":"1992","journal-title":"J. Comp. Neurol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"228","DOI":"10.12688\/f1000research.5369.1","article-title":"A novel mouse model of creatine transporter deficiency","volume":"3","author":"Baroncelli","year":"2014","journal-title":"F1000Res"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"4186","DOI":"10.1093\/hmg\/ddw252","article-title":"A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging","volume":"25","author":"Baroncelli","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.nbd.2013.11.010","article-title":"Fluoxetine in adulthood normalizes GABA release and rescues hippocampal synaptic plasticity and spatial memory in a mouse model of down syndrome","volume":"63","author":"Begenisic","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1007\/s00726-011-0852-z","article-title":"Creatine deficiency syndromes and the importance of creatine synthesis in the brain","volume":"40","author":"Braissant","year":"2011","journal-title":"Amino Acids"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1007\/s11011-018-0197-3","article-title":"Treatment outcome of creatine transporter deficiency: international retrospective cohort study","volume":"33","author":"Bruun","year":"2018","journal-title":"Metab. Brain Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1186\/1750-1172-7-96","article-title":"Screening for primary creatine deficiencies in French patients with unexplained neurological symptoms","volume":"7","author":"Cheillan","year":"2012","journal-title":"Orphanet J. Rare Dis."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1471-2105-14-128","article-title":"Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool","volume":"14","author":"Chen","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e140173","DOI":"10.1172\/jci.insight.140173","article-title":"Creatine transporter deficiency impairs stress adaptation and brain energetics homeostasis","volume":"6","author":"Chen","year":"2021","journal-title":"JCI Insight"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"11427","DOI":"10.1523\/JNEUROSCI.2492-16.2016","article-title":"The role of epigenetic mechanisms in the regulation of gene expression in the nervous system","volume":"36","author":"Cholewa-Waclaw","year":"2016","journal-title":"J. Neurosci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"3365","DOI":"10.1523\/JNEUROSCI.5427-08.2009","article-title":"Dynamic changes in presynaptic and axonal transport proteins combined with striatal neuroinflammation precede dopaminergic neuronal loss in a rat model of AAV alpha-synucleinopathy","volume":"29","author":"Chung","year":"2009","journal-title":"J. Neurosci."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1007\/s00439-006-0162-9","article-title":"X-linked creatine transporter (SLC6A8) mutations in about 1% of males with mental retardation of unknown etiology","volume":"119","author":"Clark","year":"2006","journal-title":"Hum. Genet."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"215","DOI":"10.3389\/fnmol.2017.00215","article-title":"An LMNB1 duplication caused adult-onset autosomal dominant Leukodystrophy in Chinese family: clinical manifestations, neuroradiology and genetic diagnosis","volume":"10","author":"Dai","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1156","DOI":"10.1038\/nn.3786","article-title":"Alzheimer's disease: early alterations in brain DNA methylation at ANK1, BIN1, RHBDF2 and other loci","volume":"17","author":"De Jager","year":"2014","journal-title":"Nat. Neurosci."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.gene.2015.04.011","article-title":"Estimated carrier frequency of creatine transporter deficiency in females in the general population using functional characterization of novel missense variants in the SLC6A8 gene","volume":"565","author":"Des Roches","year":"2015","journal-title":"Gene"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1002\/acn3.198","article-title":"De novo mutations in KIF1A cause progressive encephalopathy and brain atrophy","volume":"2","author":"Esmaeeli Nieh","year":"2015","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.psychres.2008.07.012","article-title":"Region and diagnosis-specific changes in synaptic proteins in schizophrenia and bipolar I disorder","volume":"178","author":"Gray","year":"2010","journal-title":"Psychiatry Res."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"560074","DOI":"10.3389\/fimmu.2020.560074","article-title":"M1 polarization markers are Upregulated in basal-like breast cancer molecular subtype and associated with favorable patient outcome","volume":"11","author":"Hachim","year":"2020","journal-title":"Front. Immunol."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1002\/mrdd.10023","article-title":"The phenotypic consequences of MECP2 mutations extend beyond Rett syndrome","volume":"8","author":"Hammer","year":"2002","journal-title":"Ment. Retard. Dev. Disabil. Res. Rev."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1038\/leu.2010.118","article-title":"Differential expression of NF-kappa B target genes in MALT lymphoma with and without chromosome translocation: insights into molecular mechanism","volume":"24","author":"Hamoudi","year":"2010","journal-title":"Leukemia"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/85132","article-title":"PLC-beta 1, activated via mGluRs, mediates activity-dependent differentiation in cerebral cortex","volume":"4","author":"Hannan","year":"2001","journal-title":"Nat. Neurosci."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"2637","DOI":"10.1002\/pmic.201400157","article-title":"N-terminomics and proteogenomics, getting off to a good start","volume":"14","author":"Hartmann","year":"2014","journal-title":"Proteomics"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"2985","DOI":"10.1111\/j.1460-9568.2005.04510.x","article-title":"Bi-directional regulation of postsynaptic cortactin distribution by BDNF and NMDA receptor activity","volume":"22","author":"Iki","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.pediatrneurol.2015.05.006","article-title":"Treatment of Creatine transporter (SLC6A8) deficiency with Oral S-Adenosyl methionine as adjunct to L-arginine, glycine, and Creatine supplements","volume":"53","author":"Jaggumantri","year":"2015","journal-title":"Pediatr. Neurol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"2936","DOI":"10.1128\/MCB.26.8.2936-2946.2006","article-title":"NF-kappa B regulates spatial memory formation and synaptic plasticity through protein kinase a\/CREB signaling","volume":"26","author":"Kaltschmidt","year":"2006","journal-title":"Mol. Cell. Biol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"2693","DOI":"10.1002\/glia.23879","article-title":"FABP7 upregulation induces a neurotoxic phenotype in astrocytes","volume":"68","author":"Killoy","year":"2020","journal-title":"Glia"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.neuron.2011.12.020","article-title":"Motor protein KIF1A is essential for hippocampal synaptogenesis and learning enhancement in an enriched environment","volume":"73","author":"Kondo","year":"2012","journal-title":"Neuron"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","article-title":"Enrichr: a comprehensive gene set enrichment analysis web server 2016 update","volume":"44","author":"Kuleshov","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1002\/humu.22709","article-title":"De novo mutations in the motor domain of KIF1A cause cognitive impairment, spastic paraparesis, axonal neuropathy, and cerebellar atrophy","volume":"36","author":"Lee","year":"2015","journal-title":"Hum. Mutat."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/1750-1326-7-47","article-title":"Ikappa Balpha deficiency in brain leads to elevated basal neuroinflammation and attenuated response following traumatic brain injury: implications for functional recovery","volume":"7","author":"Lian","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s12079-012-0182-2","article-title":"Phosphoinositide-specific phospholipase C \u03b21 gene deletion in bipolar disorder affected patient","volume":"7","author":"Lo Vasco","year":"2013","journal-title":"J. Cell Commun. Signal"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/978-3-642-45106-5_9","article-title":"BDNF and synaptic plasticity, cognitive function, and dysfunction","volume":"220","author":"Lu","year":"2014","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1002\/hipo.20900","article-title":"Increased adult hippocampal neurogenesis and abnormal migration of adult-born granule neurons is associated with hippocampal-specific cognitive deficits in phospholipase C-beta 1 knockout mice","volume":"22","author":"Manning","year":"2012","journal-title":"Hippocampus"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1126\/science.1098180","article-title":"Sites of neocortical reorganization critical for remote spatial memory","volume":"305","author":"Maviel","year":"2004","journal-title":"Science"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"fcaa089","DOI":"10.1093\/braincomms\/fcaa089","article-title":"Novel translational phenotypes and biomarkers for creatine transporter deficiency","volume":"2","author":"Mazziotti","year":"2020","journal-title":"Brain Commun"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1038\/nn1110","article-title":"NF-kappa B functions in synaptic signaling and behavior","volume":"6","author":"Meffert","year":"2003","journal-title":"Nat. Neurosci."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"2547","DOI":"10.1093\/bioinformatics\/btl412","article-title":"Variance stabilization and normalization for one-color microarray data using a data-driven multiscale approach","volume":"22","author":"Motakis","year":"2006","journal-title":"Bioinformatics"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1038\/jhg.2015.108","article-title":"De novo KIF1A mutations cause intellectual deficit, cerebellar atrophy, lower limb spasticity and visual disturbance","volume":"60","author":"Ohba","year":"2015","journal-title":"J. Hum. Genet."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1080\/19491034.2016.1260799","article-title":"Lamin B1 mediated demyelination: linking Lamins, lipids and Leukodystrophies","volume":"7","author":"Padiath","year":"2016","journal-title":"Nucleus"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"3732","DOI":"10.1093\/hmg\/ddv117","article-title":"Germline recessive mutations in PI4KA are associated with perisylvian polymicrogyria, cerebellar hypoplasia and arthrogryposis","volume":"24","author":"Pagnamenta","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.mcn.2012.05.007","article-title":"IgSF8: a developmentally and functionally regulated cell adhesion molecule in olfactory sensory neuron axons and synapses","volume":"50","author":"Ray","year":"2012","journal-title":"Mol. Cell. Neurosci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"100771","DOI":"10.1016\/j.jbior.2020.100771","article-title":"Location-dependent role of phospholipase C signaling in the brain: physiology and pathology","volume":"79","author":"Rusciano","year":"2021","journal-title":"Adv. Biol. Regul."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1086\/320595","article-title":"X-linked creatine-transporter gene (SLC6A8) defect: a new creatine-deficiency syndrome","volume":"68","author":"Salomons","year":"2001","journal-title":"Am. J. Hum. Genet."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0074-7742(08)60346-3","article-title":"The cerebrocerebellar system","volume":"41","author":"Schmahmann","year":"1997","journal-title":"Int. Rev. Neurobiol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1002\/ajmg.b.30016","article-title":"MECP2 structural and 3'-UTR variants in schizophrenia, autism and other psychiatric diseases: a possible association with autism","author":"Shibayama","year":"2004","journal-title":"Am. J. Med. Genet. B Neuropsychiatr. Genet."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/978-1-4020-6486-9_8","article-title":"Cerebral creatine deficiency syndromes: clinical aspects, treatment and pathophysiology","volume":"46","author":"Stockler","year":"2007","journal-title":"Subcell. Biochem."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"e1005562","DOI":"10.1371\/journal.pcbi.1005562","article-title":"ROTS: an R package for reproducibility-optimized statistical testing","volume":"13","author":"Suomi","year":"2017","journal-title":"PLoS Comput. Biol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1111\/jns.12235","article-title":"A de novo dominant mutation in KIF1A associated with axonal neuropathy, spasticity and autism spectrum disorder","volume":"22","author":"Tomaselli","year":"2017","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"5173","DOI":"10.1021\/jm400545n","article-title":"Synthesis and biological evaluation of new Creatine fatty esters revealed dodecyl Creatine Ester as a promising drug candidate for the treatment of the Creatine transporter deficiency","volume":"56","author":"Trotier-Faurion","year":"2013","journal-title":"J. Med. Chem."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"185","DOI":"10.2217\/nnm.13.205","article-title":"Dodecyl creatine ester and lipid nanocapsule: a double strategy for the treatment of creatine transporter deficiency","volume":"10","author":"Trotier-Faurion","year":"2015","journal-title":"Nanomedicine"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.2217\/nnm-2019-0059","article-title":"Dodecyl creatine ester-loaded nanoemulsion as a promising therapy for creatine transporter deficiency","volume":"14","author":"Ullio-Gamboa","year":"2019","journal-title":"Nanomedicine"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s10545-012-9495-9","article-title":"Functional and electrophysiological characterization of four non-truncating mutations responsible for creatine transporter (SLC6A8) deficiency syndrome","volume":"36","author":"Valayannopoulos","year":"2013","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s10545-014-9713-8","article-title":"X-linked creatine transporter deficiency: clinical aspects and pathophysiology","volume":"37","author":"van de Kamp","year":"2014","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/j.jpsychires.2011.10.011","article-title":"Expression of PSA-NCAM and synaptic proteins in the amygdala of psychiatric disorder patients","volume":"46","author":"Varea","year":"2012","journal-title":"J. Psychiatr. Res."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"e968","DOI":"10.1002\/mgg3.968","article-title":"Rett and Rett-like syndrome: expanding the genetic spectrum to KIF1A and GRIN1 gene","volume":"7","author":"Wang","year":"2019","journal-title":"Mol. Genet. Genomic Med."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/humu.1144","article-title":"Genetic and clinical aspects of X-linked hydrocephalus (L1 disease): mutations in the L1CAM gene","volume":"18","author":"Weller","year":"2001","journal-title":"Hum. Mutat."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s13229-017-0157-5","article-title":"Identification of autism-related MECP2 mutations by whole-exome sequencing and functional validation","volume":"8","author":"Wen","year":"2017","journal-title":"Mol. Autism."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.jbior.2015.11.003","article-title":"Primary phospholipase C and brain disorders","volume":"61","author":"Yang","year":"2016","journal-title":"Adv. Biol. Regul."}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2023.1118707\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,31]],"date-time":"2023-03-31T13:40:15Z","timestamp":1680270015000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2023.1118707\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,24]]},"references-count":62,"alternative-id":["10.3389\/fnmol.2023.1118707"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2023.1118707","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,24]]},"article-number":"1118707"}}