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

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.

Pubmed ID: 21623373

Authors

  • Gehman LT
  • Stoilov P
  • Maguire J
  • Damianov A
  • Lin CH
  • Shiue L
  • Ares M
  • Mody I
  • Black DL

Journal

Nature genetics

Publication Data

July 28, 2011

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM049369
  • Agency: NIGMS NIH HHS, Id: R01 GM049369
  • Agency: NIGMS NIH HHS, Id: R01 GM049369-17
  • Agency: NIGMS NIH HHS, Id: R01 GM049662
  • Agency: NIGMS NIH HHS, Id: R01 GM049662-17
  • Agency: NIGMS NIH HHS, Id: R01 GM084317
  • Agency: NIGMS NIH HHS, Id: R01 GM084317
  • Agency: NIGMS NIH HHS, Id: R01 GM084317-04
  • Agency: NIGMS NIH HHS, Id: R01 GM49662
  • Agency: NIMH NIH HHS, Id: R01 MH076994
  • Agency: NIMH NIH HHS, Id: R01 MH076994
  • Agency: NIMH NIH HHS, Id: R01 MH076994-05
  • Agency: NINDS NIH HHS, Id: R37 NS030549
  • Agency: NINDS NIH HHS, Id: R37 NS030549-15
  • Agency: NINDS NIH HHS, Id: R37 NS30549
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Alternative Splicing
  • Animals
  • Apoptosis
  • Biological Markers
  • Blotting, Western
  • Brain
  • Cell Proliferation
  • Electrophysiology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Immunoenzyme Techniques
  • Kainic Acid
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger
  • RNA-Binding Proteins
  • Reverse Transcriptase Polymerase Chain Reaction
  • Seizures
  • Synaptic Transmission