title: The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain.
abstract: The Rbfox family of RNA binding proteins regulates alternative splicing of many important neuronal transcripts, but its role in neuronal physiology is not clear. We show here that central nervous system-specific deletion of the gene encoding Rbfox1 results in heightened susceptibility to spontaneous and kainic acid-induced seizures. Electrophysiological recording revealed a corresponding increase in neuronal excitability in the dentate gyrus of the knockout mice. Whole-transcriptome analyses identified multiple splicing changes in the Rbfox1(-/-) brain with few changes in overall transcript abundance. These splicing changes alter proteins that mediate synaptic transmission and membrane excitation. Thus, Rbfox1 directs a genetic program required in the prevention of neuronal hyperexcitation and seizures. The Rbfox1 knockout mice provide a new model to study the post-transcriptional regulation of synaptic function.
authors.affiliation: Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA.
authors.forename: Lauren T
authors.initials: LT
authors.lastname: Gehman
authors.forename: Peter
authors.initials: P
authors.lastname: Stoilov
authors.forename: Jamie
authors.initials: J
authors.lastname: Maguire
authors.forename: Andrey
authors.initials: A
authors.lastname: Damianov
authors.forename: Chia-Ho
authors.initials: CH
authors.lastname: Lin
authors.forename: Lily
authors.initials: L
authors.lastname: Shiue
authors.forename: Manuel
authors.initials: M
authors.lastname: Ares
authors.forename: Istvan
authors.initials: I
authors.lastname: Mody
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Black
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D004594:Electrophysiology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007124:Immunoenzyme Techniques; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D000072260:RNA Splicing Factors; D012333:RNA, Messenger / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced; D009435:Synaptic Transmission
chemical_list: D015415:Biomarkers; D000072260:RNA Splicing Factors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C465036:Rbfox1 protein, mouse; D007608:Kainic Acid