Functional analysis of epilepsy-associated GABA_A receptor mutations using Caenorhabditis elegans.

ABSTRACT:

Objective

GABA_A receptor subunit mutations pose a significant risk for genetic generalized epilepsy; however, there are over 150 identified variants, many with unknown or unvalidated pathogenicity. We aimed to develop in vivo models for testing GABA_A receptor variants using the model organism, Caenorhabditis elegans.

Methods

CRISPR-Cas9 gene editing was used to create a complete deletion of unc-49, a C. elegans GABA_A receptor, and to create homozygous epilepsy-associated mutations in the endogenous unc-49 gene. The unc-49 deletion strain was rescued with transgenes for either the C. elegans unc-49B subunit or the α1, β3, and γ2 subunits for the human GABA_A receptor. All newly created strains were analyzed for phenotype and compared

SUBMITTER: Gadhia A 

PROVIDER: S-EPMC11296113 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature