Arfgef1 haploinsufficiency in mice alters neuronal endosome composition and decreases membrane surface postsynaptic GABA_A receptors.

ABSTRACT: ARFGEF1 encodes a guanine exchange factor involved in intracellular vesicle trafficking, and is a candidate gene for childhood genetic epilepsies. To model ARFGEF1 haploinsufficiency observed in a recent Lennox Gastaut Syndrome patient, we studied a frameshift mutation (Arfgef1^fs) in mice. Arfgef1^fs/+ pups exhibit signs of developmental delay, and Arfgef1^fs/+ adults have a significantly decreased threshold to induced seizures but do not experience spontaneous seizures. Histologically, the Arfgef1^fs/+ brain exhibits a disruption in the apical lining of the dentate gyrus and altered spine morphology of deep layer neurons. In primary hippocampal neuron culture, dendritic surface and synaptic but not total GABA_A receptors (GABA_A

SUBMITTER: Teoh J 

PROVIDER: S-EPMC6980672 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature