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RBFOX3/NeuN is Required for Hippocampal Circuit Balance and Function

RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decr...

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Detalles Bibliográficos
Autores principales: Wang, Han-Ying, Hsieh, Pei-Fen, Huang, De-Fong, Chin, Pey-Shyuan, Chou, Chih-Hsuan, Tung, Chun-Che, Chen, Shin-Yuan, Lee, Li-Jen, Gau, Susan Shur-Fen, Huang, Hsien-Sung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664964/
https://www.ncbi.nlm.nih.gov/pubmed/26619789
http://dx.doi.org/10.1038/srep17383
Descripción
Sumario:RBFOX3 mutations are linked to epilepsy and cognitive impairments, but the underlying pathophysiology of these disorders is poorly understood. Here we report replication of human symptoms in a mouse model with disrupted Rbfox3. Rbfox3 knockout mice displayed increased seizure susceptibility and decreased anxiety-related behaviors. Focusing on hippocampal phenotypes, we found Rbfox3 knockout mice showed increased expression of plasticity genes Egr4 and Arc, and the synaptic transmission and plasticity were defective in the mutant perforant pathway. The mutant dentate granules cells exhibited an increased frequency, but normal amplitude, of excitatory synaptic events, and this change was associated with an increase in the neurotransmitter release probability and dendritic spine density. Together, our results demonstrate anatomical and functional abnormality in Rbfox3 knockout mice, and may provide mechanistic insights for RBFOX3-related human brain disorders.