title: Brain-specific Foxp1 deletion impairs neuronal development and causes autistic-like behaviour.
abstract: Neurodevelopmental disorders are multi-faceted and can lead to intellectual disability, autism spectrum disorder and language impairment. Mutations in the Forkhead box FOXP1 gene have been linked to all these disorders, suggesting that it may play a central role in various cognitive and social processes. To understand the role of Foxp1 in the context of neurodevelopment leading to alterations in cognition and behaviour, we generated mice with a brain-specific Foxp1 deletion (Nestin-Cre(Foxp1-/-)mice). The mutant mice were viable and allowed for the first time the analysis of pre- and postnatal neurodevelopmental phenotypes, which included a pronounced disruption of the developing striatum and more subtle alterations in the hippocampus. More detailed analysis in the CA1 region revealed abnormal neuronal morphogenesis that was associated with reduced excitability and an imbalance of excitatory to inhibitory input in CA1 hippocampal neurons in Nestin-Cre(Foxp1-/-) mice. Foxp1 ablation was also associated with various cognitive and social deficits, providing new insights into its behavioural importance.
authors.affiliation: 1] Department of Molecular Human Genetics, Medical Faculty of Heidelberg University, Im Neuenheimer Feld 366, Heidelberg, Germany [2] Interdisciplinary Centre for Neurosciences (IZN), University of Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Bacon
authors.affiliation: Research Group Developmental Neuropsychopharmacology, Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schneider
authors.affiliation: 1] Interdisciplinary Centre for Neurosciences (IZN), University of Heidelberg, Germany [2] Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, Germany [3] INSERM UMR-S 839, University Pierre and Marie Curie, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Le Magueresse
authors.affiliation: 1] Department of Molecular Human Genetics, Medical Faculty of Heidelberg University, Im Neuenheimer Feld 366, Heidelberg, Germany [2] Interdisciplinary Centre for Neurosciences (IZN), University of Heidelberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Froehlich
authors.affiliation: Medical Research Center, University of Heidelberg, Theodor_Kutzer_Ufer 1-3, Mannheim, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Sticht
authors.affiliation: Research Group Developmental Neuropsychopharmacology, Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Gluch
authors.affiliation: 1] Interdisciplinary Centre for Neurosciences (IZN), University of Heidelberg, Germany [2] Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Monyer
authors.affiliation: 1] Department of Molecular Human Genetics, Medical Faculty of Heidelberg University, Im Neuenheimer Feld 366, Heidelberg, Germany [2] Interdisciplinary Centre for Neurosciences (IZN), University of Heidelberg, Germany.
authors.forename: G A
authors.initials: GA
authors.lastname: Rappold
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D000831:Animals, Newborn; D001321:Autistic Disorder / Q000235:genetics*; D001921:Brain / Q000254:growth & development / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics; D003712:Dendrites / Q000473:pathology; D002658:Developmental Disabilities / Q000235:genetics* / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000172:deficiency* / Q000235:genetics; D006624:Hippocampus / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D008569:Memory Disorders / Q000235:genetics; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000473:pathology / Q000502:physiology; D065808:Prepulse Inhibition / Q000235:genetics; D012097:Repressor Proteins / Q000172:deficiency* / Q000235:genetics; D012920:Social Behavior Disorders / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics
chemical_list: D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; D012097:Repressor Proteins