Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion
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...
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00111/full |
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| author | 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 |
| author_facet | 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 |
| author_sort | Tian-Jia Song |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T15:54:22Z |
| format | Article |
| id | doaj.art-651d98408f8040608bce28430ad2c663 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-22T15:54:22Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-651d98408f8040608bce28430ad2c6632022-12-21T18:20:49ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-03-011310.3389/fncel.2019.00111446274Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 DeletionTian-Jia Song0Tian-Jia Song1Tian-Jia Song2Xing-Yu Lan3Xing-Yu Lan4Xing-Yu Lan5Meng-Ping Wei6Meng-Ping Wei7Fu-Jun Zhai8Fu-Jun Zhai9Fu-Jun Zhai10Tobias M. Boeckers11Jia-Nan Wang12Jia-Nan Wang13Jia-Nan Wang14Shuo Yuan15Shuo Yuan16Shuo Yuan17Meng-Ying Jin18Meng-Ying Jin19Meng-Ying Jin20Yu-Fei Xie21Yu-Fei Xie22Yu-Fei Xie23Wan-Wen Dang24Wan-Wen Dang25Wan-Wen Dang26Chen Zhang27Chen Zhang28Michael Schön29Pei-Wen Song30Mei-Hong Qiu31Ya-Yue Song32Song-Ping Han33Ji-Sheng Han34Ji-Sheng Han35Ji-Sheng Han36Rong Zhang37Rong Zhang38Rong Zhang39Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, ChinaNeuroscience Research Institute, Peking University, Beijing, ChinaKey laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, ChinaNeuroscience Research Institute, Peking University, Beijing, ChinaKey laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, School of Life Sciences, Peking University-IDG/McGovern Institute for Brain Research, Peking University, Beijing, ChinaDepartment of Neurobiology, Capital Medical University, Beijing, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, ChinaNeuroscience Research Institute, Peking University, Beijing, ChinaKey laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, ChinaInstitute for Anatomy and Cell Biology, Ulm University, Ulm, GermanyDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, ChinaNeuroscience Research Institute, Peking University, Beijing, ChinaKey laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, ChinaNeuroscience Research Institute, Peking University, Beijing, ChinaKey laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, ChinaNeuroscience Research Institute, Peking University, Beijing, ChinaKey laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, ChinaNeuroscience Research Institute, Peking University, Beijing, ChinaKey laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, ChinaNeuroscience Research Institute, Peking University, Beijing, ChinaKey laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, ChinaState Key Laboratory of Membrane Biology, School of Life Sciences, Peking University-IDG/McGovern Institute for Brain Research, Peking University, Beijing, ChinaDepartment of Neurobiology, Capital Medical University, Beijing, ChinaInstitute for Anatomy and Cell Biology, Ulm University, Ulm, GermanyDepartment of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, ChinaSchool of Basic Medical Sciences, Tianjin Medical University, Tianjin, ChinaWuxi HANS Health Medical Technology Co., Ltd., Wuxi, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, ChinaNeuroscience Research Institute, Peking University, Beijing, ChinaKey laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, ChinaDepartment of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, ChinaNeuroscience Research Institute, Peking University, Beijing, ChinaKey laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, ChinaMutations 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.https://www.frontiersin.org/article/10.3389/fncel.2019.00111/fullShank3Phelan-McDermid syndromeautism spectrum disordersintellectual disabilitiessocial memorypain threshold |
| spellingShingle | 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 Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion Frontiers in Cellular Neuroscience Shank3 Phelan-McDermid syndrome autism spectrum disorders intellectual disabilities social memory pain threshold |
| title | Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion |
| title_full | Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion |
| title_fullStr | Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion |
| title_full_unstemmed | Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion |
| title_short | Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion |
| title_sort | altered behaviors and impaired synaptic function in a novel rat model with a complete shank3 deletion |
| topic | Shank3 Phelan-McDermid syndrome autism spectrum disorders intellectual disabilities social memory pain threshold |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00111/full |
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