Conditional Knockout of Slc35a2 Reveals Cell Autonomous Contributions to Seizures
Loading...
Date
2025-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
Brain-restricted, somatic variants in SLC35A2 have been identified in patients with medically refractory epilepsy, yet the underlying pathogenesis remains unknown. This project aims to characterize the deficits resulting from loss of Slc35a2 and investigate potential mechanisms contributing to epileptogenesis. To explore these aims, we generated a conditional knockout mouse model to assess the consequences of gene loss in vivo. Additionally, primary cortical cultures were derived from these mice to examine cell-autonomous effects and establish a tractable system for studying neuronal activity and glycosylation deficits. Here we show that Slc35a2 conditional knockout (cKO) mice exhibit reduced survival and developmental delay. These mice also show spontaneous seizure activity in vivo, indicating a strong seizure phenotype. Primary cortical neurons from Slc35a2 cKO males display aberrant network activity, suggesting a cell-autonomous contribution to epileptogenesis. Lectin staining of cultured neurons reveals glycosylation deficits, implicating glycosylation in maintaining neuronal activity. These findings provide critical insights into the mechanisms underlying Slc35a2-related epileptogenesis and highlight potential targets for therapeutic intervention in medically refractory epilepsy.
Description
Keywords
SLC35A2, Somatic mutation, Epileptogenesis, Conditional knockout mice, Glycosylation, Network Activity