Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/31645
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
Equipe AVENIR
Univ Washington
Keywords: Sodium channel
SCN1A
GEFS
SMEI
Epilepsy
Mutation
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.
URI: http://repositorio.unifesp.br/handle/11600/31645
ISSN: 0969-9961
Other Identifiers: http://dx.doi.org/10.1016/j.nbd.2009.04.007
Appears in Collections:Em verificação - Geral

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