Alterations in GABA(A) receptors in MGLUR4(-/-) mice

摘要

Disruption of the mGluR4 gene results in resistance to GABAAR antagonist-induced absence seizures. In this thesis, mGluR4-/- mice displayed 43.5% less [35S]TBPS binding, a GABAAR antagonist. Immunoblotting revealed extra bands in mGluR4-/- mice---possible abnormal GABAAR subunits. The mGluR4 gene was mapped to human chromosome 6p21.3 by FISH, to determine if it was near and potentially altered expression of GABAAR subunits. No GABAAR subunits are near mGluR4. The gene falls within a juvenile myoclonic epilepsy susceptibility locus. Protein interactions between mGluR4 and GABAAR were investigated by immunoprecipitation from rat brain. GABAAR alpha1, alpha6, and beta2 subunits were not detected in mGluR4 immunoprecipitate. beta2, but not mGluR4, was detected in alpha1 and alpha6 immunopreciptates from rat brain.