Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

A BAC transgenic mouse model reveals neuron subtype-specific effects of a Generalized Epilepsy with Febrile Seizures Plus (GEFS plus ) mutation

Texto completo
Autor(es):
Mostrar menos -
Tang, Bin [1] ; Dutt, Karoni [2] ; Papale, Ligia [3, 1] ; Rusconi, Raffaella [4] ; Shankar, Anupama [1] ; Hunter, Jessica [1] ; Tufik, Sergio [3] ; Yu, Frank H. [5] ; Catterall, William A. [5] ; Mantegazza, Massimo [4, 6] ; Goldin, Alan L. [2, 7] ; Escayg, Andrew [1]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Emory Univ, Dept Human Genet, Atlanta, GA 30322 - USA
[2] Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 - USA
[3] Univ Fed Sao Paulo, Dept Psychobiol, Sao Paulo - Brazil
[4] Ist Neurolog Besta, Dept Neurophysiopathol, I-20133 Milan - Italy
[5] Univ Washington, Dept Pharmacol, Seattle, WA 98195 - USA
[6] Equipe AVENIR, IFR 95 Paris 5, F-75006 Paris - France
[7] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 - USA
Número total de Afiliações: 7
Tipo de documento: Artigo Científico
Fonte: Neurobiology of Disease; v. 35, n. 1, p. 91-102, JUL 2009.
Citações Web of Science: 68
Resumo

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. (AU)

Processo FAPESP: 98/14303-3 - Center for Sleep Studies
Beneficiário:Sergio Tufik
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs