2. Academic Validation
  3. 16p11.2 CNV gene Doc2α functions in neurodevelopment and social behaviors through interaction with Secretagogin

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

  • Cell Rep. 2023 Jun 22;42(7):112691. doi: 10.1016/j.celrep.2023.112691.
Qiu-Wen Wang 1,  Junhong Qin 2,  Yan-Fen Chen 1,  Yingfeng Tu 2,  Yun-Yun Xing 3,  Yuchen Wang 4,  Lv-Yu Yang 1,  Si-Yao Lu 3,  Libo Geng 3,  Wei Shi 5,  Yiming Yang 6,  Jun Yao 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 2 Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 3 Jiangsu Key Laboratory of Language and Cognitive Neuroscience, School of Linguistic Sciences and Arts, Jiangsu Normal University, Xuzhou 221116, China; Jiangsu Collaborative Innovation Center for Language Ability, Xuzhou 221009, China.
  • 4 School of Engineering Medicine and School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
  • 5 School of Engineering Medicine and School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China. Electronic address: [email protected].
  • 6 Jiangsu Key Laboratory of Language and Cognitive Neuroscience, School of Linguistic Sciences and Arts, Jiangsu Normal University, Xuzhou 221116, China; Jiangsu Collaborative Innovation Center for Language Ability, Xuzhou 221009, China. Electronic address: [email protected].
  • 7 State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, IDG/McGovern Institute for Brain Research, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: [email protected].
PMID: 37354460 DOI: 10.1016/j.celrep.2023.112691
Abstract

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.

Keywords

16p11.2; CP: Developmental biology; CP: Neuroscience; Doc2α; SCGN; neurodevelopmental disorder; social behavior.

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