Spontaneous seizure and memory loss in mice expressing an epileptic encephalopathy variant in the calmodulin-binding domain of K <sub>v</sub> 7.2
Eung Chang Kim, Jiaren Zhang, Andy Y. Tang, Eric C. Bolton, Justin S. Rhodes, Catherine A. Christian, Hee Jung Chung
Abstract
Significance Epileptic encephalopathy (EE) is a devastating neurologic disorder characterized by early-onset seizures with severe cognitive and psychomotor impairments. EE is associated with dominant mutations in the KCNQ2 gene which encodes the K v 7.2 subunit of K v 7 potassium channels. Previously, we reported that multiple EE mutations in the intracellular calmodulin-binding domain of K v 7.2 decreased surface expression of axonal K v 7 channels critical for suppressing neuronal excitability. Here, we generated conditional knockin mice carrying one of these mutations, M547V. These mice displayed spontaneous seizures, cognitive impairment, neurodegeneration, and reactive astrogliosis, implicating abnormal K v 7 surface expression as a key etiology of KCNQ2 -associated EE.