Mechanistic insights from a mouse model of HCN1 developmental epileptic encephalopathy
Wednesday, August 18, 2021
16:00 UTC
Prof Christopher Reid
The Florey Institute of Neuroscience and Mental Health
Recording
Open recording
Hosted by Clinical and Experimental Epilepsy70 minutes
Abstract
Pathogenic variants in HCN1 are associated with severe developmental and epileptic encephalopathies (DEE). We have engineered the Hcn1 M294L heterozygous knock-in (Hcn1M294L) mouse which is a homolog of the de novo HCN1 M305L recurrent pathogenic variant. The mouse recapitulates the phenotypic features of patients including having spontaneous seizures and a learning deficit. In this talk I will present experimental work that probes the molecular and cellular mechanisms underlying hyper-excitability in the mouse model. This will include testing the efficacy of currently available antiepileptic drugs and a novel precision medicine approach. I will also briefly touch on how disease biology can give insights into the biophysical properties of HCN channels.
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