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Nat Genet. 2011 May 29;43(7):706-11. doi: 10.1038/ng.841.

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

Author information

1
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, USA.

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.

PMID:
21623373
PMCID:
PMC3125461
DOI:
10.1038/ng.841
[Indexed for MEDLINE]
Free PMC Article

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