RARE DISEASE RESEARCH & TRAINING

IPRD funded research by Yi Zhou, Ph.D.

Developmental and Epileptic Encephalopathies (DEEs) are a group of rare pediatric seizures accompanied by developmental delay and intellectual disability. The majority of DEEs are associated with inherited or de novo mutations of a heterogeneous group of genes. Recent evidence shows that mutations of the YWHAG gene may be a causal factor for DEE. However, how YWHAG mutations cause childhood epilepsy and hinder intellectual development is not known. YWHAG encodes the gamma isoform of 14-3-3, a family of homologous signaling proteins that are abundantly expressed in the brain and implicated in a number of neurological and neuropsychiatric disorders. We have developed and characterized several genetic and viral-mediated 14-3-3 mouse models, and demonstrated that deficiency of all 14-3-3 isoforms in mouse brains results in various alterations at molecular, synaptic and behavioral levels. In this project, we will develop and validate novel animal and human cellular models of disease-associated YWHAG mutation for investigation of the molecular and neurobiological bases of DEEs.