title: Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects.
abstract: The NONO protein has been characterized as an important transcriptional regulator in diverse cellular contexts. Here we show that loss of NONO function is a likely cause of human intellectual disability and that NONO-deficient mice have cognitive and affective deficits. Correspondingly, we find specific defects at inhibitory synapses, where NONO regulates synaptic transcription and gephyrin scaffold structure. Our data identify NONO as a possible neurodevelopmental disease gene and highlight the key role of the DBHS protein family in functional organization of GABAergic synapses.
authors.affiliation: Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.|Neuromorphology Group, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
authors.forename: Dennis
authors.initials: D
authors.lastname: Mircsof
authors.affiliation: INSERM UMR 1163, Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Maéva
authors.initials: M
authors.lastname: Langouët
authors.affiliation: INSERM UMR 1163, Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.|Service de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.affiliation: INSERM UMR 1163, Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Sébastien
authors.identifier: http://orcid.org/0000-0002-8942-6731
authors.initials: S
authors.lastname: Moutton
authors.affiliation: INSERM UMR 1163, Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Siquier-Pernet
authors.affiliation: Genomic Platform, INSERM UMR 1163, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Bole-Feysot
authors.affiliation: Bioinformatic Platform, INSERM UMR 1163, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cagnard
authors.affiliation: Bioinformatic Platform, INSERM UMR 1163, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Nitschke
authors.affiliation: Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Gaspar
authors.affiliation: Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
authors.forename: Matej
authors.initials: M
authors.lastname: Žnidarič
authors.affiliation: Genomic Platform, INSERM UMR 1163, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Alibeu
authors.affiliation: Institute of Anatomy, University of Zürich and Institute of Human Movement Sciences and Sport, ETH Zürich, Switzerland.
authors.forename: Ann-Kristina
authors.initials: AK
authors.lastname: Fritz
authors.affiliation: Institute of Anatomy, University of Zürich and Institute of Human Movement Sciences and Sport, ETH Zürich, Switzerland.
authors.forename: David P
authors.initials: DP
authors.lastname: Wolfer
authors.affiliation: Molecular Imaging and Functional Pharmacology Group, University of Zürich, Zürich, Switzerland.
authors.forename: Aileen
authors.initials: A
authors.lastname: Schröter
authors.affiliation: Neuromorphology Group, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bosshard
authors.affiliation: Molecular Imaging and Functional Pharmacology Group, University of Zürich, Zürich, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Rudin
authors.affiliation: Neuromorphology Group, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
authors.forename: Christina
authors.initials: C
authors.lastname: Koester
authors.affiliation: Neuromorphology Group, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Crestani
authors.affiliation: Center for Integrative Rodent Physiology, University of Zürich, Zürich, Switzerland.
authors.forename: Petra
authors.initials: P
authors.lastname: Seebeck
authors.affiliation: INSERM UMR 1163, Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.|Service de radiologie pédiatrique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.affiliation: Yorkshire Regional Genetics Service, Leeds Teaching Hospitals National Health Service Trust, Department of Clinical Genetics, Chapel Allerton Hospital, Chapeltown Road, Leeds, UK.
authors.forename: Katrina
authors.initials: K
authors.lastname: Prescott
authors.affiliation: Tufts University, Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts, USA.
authors.forename: Rochelle
authors.initials: R
authors.lastname: Hines
authors.affiliation: Tufts University, Sackler School of Graduate Biomedical Sciences, Boston, Massachusetts, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Moss
authors.affiliation: Neuromorphology Group, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
authors.forename: Jean-Marc
authors.identifier: http://orcid.org/0000-0002-8552-3702
authors.initials: JM
authors.lastname: Fritschy
authors.affiliation: INSERM UMR 1163, Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Arnold
authors.initials: A
authors.lastname: Munnich
authors.affiliation: INSERM UMR 1163, Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.|Service de Génétique, Hôpital Necker-Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris, France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
authors.affiliation: Chronobiology and Sleep Research Group, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Brown
authors.affiliation: Neuromorphology Group, Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
authors.forename: Shiva K
authors.identifier: http://orcid.org/0000-0003-0074-1805
authors.initials: SK
authors.lastname: Tyagarajan
authors.affiliation: INSERM UMR 1163, Laboratory of Molecular and Pathophysiological Bases of Cognitive Disorders, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Necker-Enfants Malades Hospital, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Colleaux
mesh_terms: D000293:Adolescent; D000818:Animals; D001921:Brain / Q000473:pathology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D009433:Neural Inhibition / Q000235:genetics*; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics*; D050810:Octamer Transcription Factors / Q000235:genetics*; D010375:Pedigree; D016601:RNA-Binding Proteins / Q000235:genetics*; D013569:Synapses / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins