Frontiers in Cellular Neuroscience (Mar 2019)
Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion
- Tian-Jia Song,
- Tian-Jia Song,
- Tian-Jia Song,
- Xing-Yu Lan,
- Xing-Yu Lan,
- Xing-Yu Lan,
- Meng-Ping Wei,
- Meng-Ping Wei,
- Fu-Jun Zhai,
- Fu-Jun Zhai,
- Fu-Jun Zhai,
- Tobias M. Boeckers,
- Jia-Nan Wang,
- Jia-Nan Wang,
- Jia-Nan Wang,
- Shuo Yuan,
- Shuo Yuan,
- Shuo Yuan,
- Meng-Ying Jin,
- Meng-Ying Jin,
- Meng-Ying Jin,
- Yu-Fei Xie,
- Yu-Fei Xie,
- Yu-Fei Xie,
- Wan-Wen Dang,
- Wan-Wen Dang,
- Wan-Wen Dang,
- Chen Zhang,
- Chen Zhang,
- Michael Schön,
- Pei-Wen Song,
- Mei-Hong Qiu,
- Ya-Yue Song,
- Song-Ping Han,
- Ji-Sheng Han,
- Ji-Sheng Han,
- Ji-Sheng Han,
- Rong Zhang,
- Rong Zhang,
- Rong Zhang
Affiliations
- Tian-Jia Song
- Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Tian-Jia Song
- Neuroscience Research Institute, Peking University, Beijing, China
- Tian-Jia Song
- Key laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
- Xing-Yu Lan
- Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Xing-Yu Lan
- Neuroscience Research Institute, Peking University, Beijing, China
- Xing-Yu Lan
- Key laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
- Meng-Ping Wei
- State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China
- Meng-Ping Wei
- Department of Neurobiology, Capital Medical University, Beijing, China
- Fu-Jun Zhai
- Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Fu-Jun Zhai
- Neuroscience Research Institute, Peking University, Beijing, China
- Fu-Jun Zhai
- Key laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
- Tobias M. Boeckers
- Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany
- Jia-Nan Wang
- Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Jia-Nan Wang
- Neuroscience Research Institute, Peking University, Beijing, China
- Jia-Nan Wang
- Key laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
- Shuo Yuan
- Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Shuo Yuan
- Neuroscience Research Institute, Peking University, Beijing, China
- Shuo Yuan
- Key laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
- Meng-Ying Jin
- Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Meng-Ying Jin
- Neuroscience Research Institute, Peking University, Beijing, China
- Meng-Ying Jin
- Key laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
- Yu-Fei Xie
- Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Yu-Fei Xie
- Neuroscience Research Institute, Peking University, Beijing, China
- Yu-Fei Xie
- Key laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
- Wan-Wen Dang
- Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Wan-Wen Dang
- Neuroscience Research Institute, Peking University, Beijing, China
- Wan-Wen Dang
- Key laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
- Chen Zhang
- State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China
- Chen Zhang
- Department of Neurobiology, Capital Medical University, Beijing, China
- Michael Schön
- Institute for Anatomy and Cell Biology, Ulm University, Ulm, Germany
- Pei-Wen Song
- Department of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Mei-Hong Qiu
- Department of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, China
- Ya-Yue Song
- School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
- Song-Ping Han
- Wuxi HANS Health Medical Technology Co., Ltd., Wuxi, China
- Ji-Sheng Han
- Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Ji-Sheng Han
- Neuroscience Research Institute, Peking University, Beijing, China
- Ji-Sheng Han
- Key laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
- Rong Zhang
- Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China
- Rong Zhang
- Neuroscience Research Institute, Peking University, Beijing, China
- Rong Zhang
- Key laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China
- DOI
- https://doi.org/10.3389/fncel.2019.00111
- Journal volume & issue
-
Vol. 13
Abstract
Mutations within the Shank3 gene, which encodes a key postsynaptic density (PSD) protein at glutamatergic synapses, contribute to the genetic etiology of defined autism spectrum disorders (ASDs), including Phelan-McDermid syndrome (PMS) and intellectual disabilities (ID). Although there are a series of genetic mouse models to study Shank3 gene in ASDs, there are few rat models with species-specific advantages. In this study, we established and characterized a novel rat model with a deletion spanning exons 11–21 of Shank3, leading to a complete loss of the major SHANK3 isoforms. Synaptic function and plasticity of Shank3-deficient rats were impaired detected by biochemical and electrophysiological analyses. Shank3-depleted rats showed impaired social memory but not impaired social interaction behaviors. In addition, impaired learning and memory, increased anxiety-like behavior, increased mechanical pain threshold and decreased thermal sensation were observed in Shank3-deficient rats. It is worth to note that Shank3-deficient rats had nearly normal levels of the endogenous social neurohormones oxytocin (OXT) and arginine-vasopressin (AVP). This new rat model will help to further investigate the etiology and assess potential therapeutic target and strategy for Shank3-related neurodevelopmental disorders.
Keywords
- Shank3
- Phelan-McDermid syndrome
- autism spectrum disorders
- intellectual disabilities
- social memory
- pain threshold
