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Title: A BAC transgenic mouse model reveals neuron subtype-specific effects of a Generalized Epilepsy with Febrile Seizures Plus (GEFS plus ) mutation
Authors: Tang, Bin
Dutt, Karoni
Papale, Ligia [UNIFESP]
Rusconi, Raffaella
Shankar, Anupama
Hunter, Jessica
Tufik, Sergio [UNIFESP]
Yu, Frank H.
Catterall, William A.
Mantegazza, Massimo
Goldin, Alan L.
Escayg, Andrew
Emory Univ
Univ Calif Irvine
Universidade Federal de São Paulo (UNIFESP)
Ist Neurolog Besta
Univ Washington
Keywords: Sodium channel
Issue Date: 1-Jul-2009
Publisher: Elsevier B.V.
Citation: Neurobiology of Disease. San Diego: Academic Press Inc Elsevier Science, v. 35, n. 1, p. 91-102, 2009.
Abstract: Mutations in the voltage-gated sodium channel SCN1A are responsible for a number of seizure disorders including Generalized Epilepsy with Febrile Seizures Plus (GEFS+) and Severe Myoclonic Epilepsy of Infancy (SMEI). To determine the effects of SCN1A mutations on channel function in vivo, we generated a bacterial artificial chromosome (BAC) transgenic mouse model that expresses the human SCN1A GEFS+ mutation, R1648H. Mice with the R1648H mutation exhibit a more severe response to the proconvulsant kainic acid compared with mice expressing a control Scn1a transgene. Electrophysiological analysis of dissociated neurons from mice with the R1648H mutation reveal delayed recovery from inactivation and increased use-dependent inactivation only in inhibitory bipolar neurons, as well as a hyperpolarizing shift in the voltage dependence of inactivation only in excitatory pyramidal neurons. These results demonstrate that the effects of SCN1A mutations are cell type-dependent and that the R1648H mutation specifically leads to a reduction in interneuron excitability. (C) 2009 Elsevier Inc. All rights reserved.
ISSN: 0969-9961
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