iScience (Sep 2021)

Genetic and functional analysis reveals TENM4 contributes to schizophrenia

  • Xin Yi,
  • Minzhe Li,
  • Guang He,
  • Huihui Du,
  • Xingwang Li,
  • Dongmei Cao,
  • Lu Wang,
  • Xi Wu,
  • Fengping Yang,
  • Xu Chen,
  • Lin He,
  • Yong Ping,
  • Daizhan Zhou

Journal volume & issue
Vol. 24, no. 9
p. 103063

Abstract

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Summary: TENM4, 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 TENM4 in schizophrenia (SCZ) remain unclear. We identified possible pathogenic mutations in the TENM4 gene through target sequencing of TENM4 in 68 SCZ families. We further demonstrated that aberrant expression of Ten-m leads to lower learning ability, sleep reduction, and increased aggressiveness in animal models. RNA sequencing showed that aberrant expression of Ten-m was related to stimulus perception and metabolic process, and Gene Ontology enrichment terms were neurogenesis and ATPase activity. This study provides strong evidence that TENM4 contributes to SCZ, and its functional mutations might be responsible for the impaired neural circuits and behaviors observed in SCZ.

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