Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/44455
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Type: Journal article
Title: Reduced cortical inhibition in a mouse model of familial childhood absence epilepsy
Author: Tan, H.
Reid, C.
Single, F.
Davies, P.
Chiu, C.
Murphy, S.
Clarke, A.
Dibbens, L.
Krestel, H.
Mulley, J.
Jones, M.
Seeburg, P.
Sakmann, B.
Berkovic, S.
Sprengel, R.
Petrou, S.
Citation: Proceedings of the National Academy of Sciences of the United States of America, 2007; 104(44):17536-17541
Publisher: Natl Acad Sciences
Issue Date: 2007
ISSN: 0027-8424
1091-6490
Statement of
Responsibility: 
Heneu 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 Petrou
Abstract: Mutations 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.
Keywords: Animals; Mice; Epilepsy, Absence; Disease Models, Animal; Genetic Predisposition to Disease; Ethosuximide; Receptors, GABA-A; Protein Subunits; Phenotype
Rights: Copyright © 2007 by The National Academy of Sciences of the USA
RMID: 0020073473
DOI: 10.1073/pnas.0708440104
Published version: http://www.pnas.org/cgi/reprint/0708440104v1.pdf
Appears in Collections:Molecular and Biomedical Science publications

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