STXBP1 early onset encephalopathy

STXBP1 early onset encephalopathy

In humans, de novo mutations in the STXBP1 gene (alias Munc18) lead to early infantile epileptic encephalopathies that are characterized by infantile epilepsy, intellectual disability, and can include autistic features. The protein encoded by this gene plays a critical role in synaptic neurotransmitter release. Patients receive a diverse range of primary diagnosis, including Ohtahara Syndrome, Dravet syndrome and atypical Rett syndrome.

Stxbp1 mouse model

Heterozygous loss of function in Stxbp1+/-  in mice mimics symptoms seen in humans. Sylics has published this model together with collaborators (Kovacevic 2018, Brain). Learning and memory deficits are detected in a fear conditioning assay and in reversal learning on the Barnes Maze.  Stxbp1+/-  show specific changes in spontaneous behavior in PhenoTyper home cages.

Epileptic discharges the EEG of Stxbp1 model

In freely moving Stxbp1+/- mice equipped with telemetric EEG implants, an increased number of epileptic spike wave discharges was seen in particular during moments of sleep and rest. These could partially be suppressed by an anti epileptic drug (AED levetiracetam). c-Fos immunohistochemistry showed an increased number of recently active neurons, likely related to epileptic activity.

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