Genetic and functional analysis reveals TENM4 contributes to schizophrenia

Abstract

<i>TENM4</i>, encoding a member of the teneurin protein family, is a risk gene shared by many types of mental diseases and is implicated in neuronal plasticity and signaling. However, the role and the mechanisms of <i>TENM4</i> in schizophrenia (SCZ) remain unclear. We identified possible pathogenic mutations in the <i>TENM4</i> gene through target sequencing of <i>TENM4</i> in 68 SCZ families. We further demonstrated that aberrant expression of <i>Ten-m</i> leads to lower learning ability, sleep reduction, and increased aggressiveness in animal models. RNA sequencing showed that aberrant expression of <i>Ten-m</i> was related to stimulus perception and metabolic process, and Gene Ontology enrichment terms were neurogenesis and ATPase activity. This study provides strong evidence that <i>TENM4</i> contributes to SCZ, and its functional mutations might be responsible for the impaired neural circuits and behaviors observed in SCZ.