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Publication : The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain.

First Author  Gehman LT Year  2011
Journal  Nat Genet Volume  43
Issue  7 Pages  706-11
PubMed ID  21623373 Mgi Jnum  J:176189
Mgi Id  MGI:5288591 Doi  10.1038/ng.841
Citation  Gehman LT, et al. (2011) The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain. Nat Genet 43(7):706-11
abstractText  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.
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