Patient-derived SLC6A1 variant S295L results in an epileptic phenotype similar to haploinsufficient mice.

ABSTRACT: The solute carrier family 6 member 1 (SLC6A1) gene encodes GAT-1, a γ-aminobutyric acid transporter expressed on astrocytes and inhibitory neurons. Mutations in SLC6A1 are associated with epilepsy and developmental disorders, including motor and social impairments, but variant-specific animal models are needed to elucidate mechanisms. Here, we report electrocorticographic (ECoG) recordings and clinical data from a patient with a variant in SLC6A1 that encodes GAT-1 with a serine-to-leucine substitution at amino acid 295 (S295L), who was diagnosed with childhood absence epilepsy. Next, we show that mice bearing the S295L mutation (GAT-1^S295L/+ ) have spike-and-wave discharges with motor arrest consistent with absence-type seizures, similar to GAT-1^+/- mice. GAT-1^S

SUBMITTER: Lindquist BE 

PROVIDER: S-EPMC10592270 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature