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ePoster
INHIBITORY NEURON DYSFUNCTION DRIVES ENCEPHALOPATHY IN A GENETIC MODEL OF GPI ANCHOR DEFICIENCY
Qi Zhangand 7 co-authors
iGCORE
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS01-07AM-075
Presentation
Date TBA
Board: PS01-07AM-075
Event Information
Poster Board
PS01-07AM-075
Poster
View posterAbstract
Mutations in the PIGA gene cause inherited glycosylphosphatidylinositol(GPI) deficiency (IGD), a severe neurodevelopmental disorder characterized by intractable epilepsy and intellectual disability. However, the relative contributions of distinct neuronal populations to IGD pathogenesis remain poorly understood.
To address this, we generated conditional mouse models in which Piga was selectively ablated in telencephalic excitatory neurons, inhibitory neurons, or thalamic neurons. Hemizygous conditional knockout (cKO) mice with GPI deficiency in either excitatory or inhibitory neurons exhibited severe embryonic defects. In adulthood, mosaic cKO mice targeting excitatory or inhibitory neurons displayed motor dysfunction, impaired fear memory, and heightened susceptibility to kainic acid–induced seizures.
Notably, Piga ablation in inhibitory neurons resulted in particularly pronounced neuronal and synaptic abnormalities and closely recapitulated the clinical features observed in patients with severe IGD.
Together, these findings identify inhibitory neurons as a critical cellular substrate underlying IGD encephalopathy and establish cell type–specific IGD mouse models as valuable platforms for mechanistic studies and therapeutic development.
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