Journal article

Multiple molecular mechanisms for a single GABA(A) mutation in epilepsy

Christopher A Reid, Taehwan Kim, A Marie Phillips, Jun Low, Samuel F Berkovic, Bernhard Luscher, Steven Petrou

NEUROLOGY | LIPPINCOTT WILLIAMS & WILKINS | Published : 2013

Abstract

OBJECTIVE: To understand the molecular basis and differential penetrance of febrile seizures and absence seizures in patients with the γ2(R43Q) GABA receptor mutation. METHODS: Spike-and-wave discharges and thermal seizure susceptibility were measured in heterozygous GABA γ2 knock-out and GABA γ2(R43Q) knock-in mice models crossed to different mouse strains. RESULTS: By comparing the GABA γ2 knock-out with the GABA γ2(R43Q) knock-in mouse model we show that haploinsufficiency underlies the genesis of absence seizures but cannot account for the thermal seizure susceptibility. Additionally, while the expression of the absence seizure phenotype was very sensitive to mouse background genetics, t..

View full abstract

Grants

Awarded by NHMRC


Awarded by ARC


Awarded by NATIONAL INSTITUTE OF MENTAL HEALTH


Funding Acknowledgements

Supported by NHMRC project grant 628520 to C.A.R. and a NHMRC program grant 400121 to S.P. and S.F.B. S.P. acknowledges support from a NMHRC fellowship (1005050) and S.F.B. support from an NHMRC Australian Fellowship (466671). C.A.R. also acknowledges the support of an ARC Future Fellowship (FT0990628). The Angior Foundation supported the purchase of equipment. The Florey Institute of Neuroscience and Mental Health is supported by Victorian State Government infrastructure funds.