Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/44455
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dc.contributor.authorTan, H.en
dc.contributor.authorReid, C.en
dc.contributor.authorSingle, F.en
dc.contributor.authorDavies, P.en
dc.contributor.authorChiu, C.en
dc.contributor.authorMurphy, S.en
dc.contributor.authorClarke, A.en
dc.contributor.authorDibbens, L.en
dc.contributor.authorKrestel, H.en
dc.contributor.authorMulley, J.en
dc.contributor.authorJones, M.en
dc.contributor.authorSeeburg, P.en
dc.contributor.authorSakmann, B.en
dc.contributor.authorBerkovic, S.en
dc.contributor.authorSprengel, R.en
dc.contributor.authorPetrou, S.en
dc.date.issued2007en
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2007; 104(44):17536-17541en
dc.identifier.issn0027-8424en
dc.identifier.issn1091-6490en
dc.identifier.urihttp://hdl.handle.net/2440/44455-
dc.description.abstractMutations in the GABAA receptor 2 subunit are associated with childhood absence epilepsy and febrile seizures. To understand better the molecular basis of absence epilepsy in man, we developed a mouse model harboring a 2 subunit point mutation (R43Q) found in a large Australian family. Mice heterozygous for the mutation demonstrated behavioral arrest associated with 6-to 7-Hz spike-and-wave discharges, which are blocked by ethosuximide, a first-line treatment for absence epilepsy in man. Seizures in the mouse showed an abrupt onset at around age 20 days corresponding to the childhood nature of this disease. Reduced cell surface expression of 2(R43Q) was seen in heterozygous mice in the absence of any change in 1 subunit surface expression, ruling out a dominant-negative effect. GABAA-mediated synaptic currents recorded from cortical pyramidal neurons revealed a small but significant reduction that was not seen in the reticular or ventrobasal thalamic nuclei. We hypothesize that a subtle reduction in cortical inhibition underlies childhood absence epilepsy seen in humans harboring the R43Q mutation.en
dc.description.statementofresponsibilityHeneu O. Tan, Christopher A. Reid, Frank N. Single, Philip J. Davies, Cindy Chiu, Susan Murphy, Alison L. Clarke, Leanne Dibbens, Heinz Krestel, John C. Mulley, Mathew V. Jones, Peter H. Seeburg, Bert Sakmann, Samuel F. Berkovic, Rolf Sprengel and Steven Petrouen
dc.language.isoenen
dc.publisherNatl Acad Sciencesen
dc.rightsCopyright © 2007 by The National Academy of Sciences of the USAen
dc.source.urihttp://www.pnas.org/cgi/reprint/0708440104v1.pdfen
dc.subjectAnimals; Mice; Epilepsy, Absence; Disease Models, Animal; Genetic Predisposition to Disease; Ethosuximide; Receptors, GABA-A; Protein Subunits; Phenotypeen
dc.titleReduced cortical inhibition in a mouse model of familial childhood absence epilepsyen
dc.typeJournal articleen
dc.identifier.rmid0020073473en
dc.identifier.doi10.1073/pnas.0708440104en
dc.identifier.pubid47040-
pubs.library.collectionMolecular and Biomedical Science publicationsen
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
Appears in Collections:Molecular and Biomedical Science publications

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