HCN1

Mechanistic insights from a mouse model of HCN1 developmental epileptic encephalopathy

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.

Dissecting the role of HCN1 in Developmental and Epileptic Encephalopathy (DEE) by exploiting patient-specific models of cerebral cortex development in vivo

Efficacy of anti-seizure medication in a mouse model of HCN1 developmental and epileptic encephalopathy

Retinal dysfunction in a mouse model of HCN1 developmental epileptic encephalopathy