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A BAC transgenic mouse model reveals neuron subtype-specific effects of a Generalized Epilepsy with Febrile Seizures Plus (GEFS plus ) mutation
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Tang, Bin | - |
dc.contributor.author | Dutt, Karoni | - |
dc.contributor.author | Papale, Ligia | - |
dc.contributor.author | Rusconi, Raffaella | - |
dc.contributor.author | Shankar, Anupama | - |
dc.contributor.author | Hunter, Jessica | - |
dc.contributor.author | Tufik, Sergio | - |
dc.contributor.author | Yu, Frank H. | - |
dc.contributor.author | Catterall, William A. | - |
dc.contributor.author | Mantegazza, Massimo | - |
dc.contributor.author | Goldin, Alan L. | - |
dc.contributor.author | Escayg, Andrew | - |
dc.date.accessioned | 2010-07-12T06:08:35Z | - |
dc.date.available | 2010-07-12T06:08:35Z | - |
dc.date.issued | 2009-07 | - |
dc.identifier.citation | Neurobiology of Disease 35 (2009) 91-102 | en |
dc.identifier.issn | 0969-9961 | - |
dc.identifier.uri | https://hdl.handle.net/10371/68600 | - |
dc.description.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. | en |
dc.description.sponsorship | This study was supported by NIH Research Grants NS046484,
NS051834 (A.E.) and NS48336 (A.L.G.), and grants from the March of Dimes Birth Defects Foundation (#5-FY02-250) (A.E.) and the McKnight Endowment Fund for Neuroscience (A.L.G.), the European Integrated Project EPICURE (M.M.) and the Italian Telethon grant GGP07277 (M.M.). K.D. was supported by a fellowship from the Epilepsy Foundation. L.P. was supported fellowships from AFIP and FAPESP (07-50534-5). ST was supported by FAPESP (CEPID#98/14303-3). | en |
dc.language.iso | en | en |
dc.publisher | Elsevier | en |
dc.subject | Sodium channel | en |
dc.subject | SCN1A | en |
dc.subject | GEFS+ | en |
dc.subject | SMEI | en |
dc.subject | Epilepsy | en |
dc.subject | Mutation | en |
dc.title | A BAC transgenic mouse model reveals neuron subtype-specific effects of a Generalized Epilepsy with Febrile Seizures Plus (GEFS plus ) mutation | en |
dc.type | Article | en |
dc.identifier.doi | 10.1016/j.nbd.2009.04.007 | - |
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