期刊
ISCIENCE
卷 24, 期 9, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2021.103063
关键词
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资金
- National Key Research and Development Program [2016YFC0906400, 2016YFC1201700]
- National Natural Science Foundation of China [8142106, 81970999, 82071262, 81872297]
- Innovation Funding in Shanghai [20JC1418600]
- Shanghai Leading Academic Discipline Project [B205]
- Shanghai Rising-Star Program [19QA1404900]
This study identified possible pathogenic mutations in the TENM4 gene and demonstrated its association with impaired neural circuits and behaviors observed in schizophrenia through aberrant expression leading to lower learning ability, reduced sleep, and increased aggressiveness in animal models.
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 andmetabolic process, and Gene Ontology enrichment terms were neurogenesis andATPase 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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