16p11.2 CNV gene Doc2α functions in neurodevelopment and social behaviors through interaction with Secretagogin

Autor: Qiu-Wen Wang, Junhong Qin, Yan-Fen Chen, Yingfeng Tu, Yun-Yun Xing, Yuchen Wang, Lv-Yu Yang, Si-Yao Lu, Libo Geng, Wei Shi, Yiming Yang, Jun Yao
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cell Reports, Vol 42, Iss 7, Pp 112691- (2023)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2023.112691
Popis: Summary: Copy-number variations (CNVs) of the human 16p11.2 genetic locus are associated with neurodevelopmental disorders, including autism spectrum disorders (ASDs) and schizophrenia. However, it remains largely unclear how this locus is involved in the disease pathogenesis. Doc2α is localized within this locus. Here, using in vivo and ex vivo electrophysiological and morphological approaches, we show that Doc2α-deficient mice have neuronal morphological abnormalities and defects in neural activity. Moreover, the Doc2α-deficient mice exhibit social and repetitive behavioral deficits. Furthermore, we demonstrate that Doc2α functions in behavioral and neural phenotypes through interaction with Secretagogin (SCGN). Finally, we demonstrate that SCGN functions in social/repetitive behaviors, glutamate release, and neuronal morphology of the mice through its Doc2α-interacting activity. Therefore, Doc2α likely contributes to neurodevelopmental disorders through its interaction with SCGN.
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