16p11.2 CNV gene Doc2α functions in neurodevelopment and social behaviors through interaction with Secretagogin
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
Affiliations
Qiu-Wen Wang
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
Junhong Qin
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
Yan-Fen Chen
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
Yingfeng Tu
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
Yun-Yun Xing
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
Yuchen Wang
School of Engineering Medicine and School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
Lv-Yu Yang
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
Si-Yao Lu
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
Libo Geng
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
Wei Shi
School of Engineering Medicine and School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China; Corresponding author
Yiming Yang
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; Corresponding author
Jun Yao
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; Corresponding author
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.
