Song, Tian-Jia and Lan, Xing-Yu and Wei, Meng-Ping and Zhai, Fu-Jun and Boeckers, Tobias M. and Wang, Jia-Nan and Yuan, Shuo and Jin, Meng-Ying and Xie, Yu-Fei and Dang, Wan-Wen and Zhang, Chen and Schön, Michael and Song, Pei-Wen and Qiu, Mei-Hong and Song, Ya-Yue and Han, Song-Ping and Han, Ji-Sheng and Zhang, Rong (2019) Altered Behaviors and Impaired Synaptic Function in a Novel Rat Model With a Complete Shank3 Deletion. Frontiers in Cellular Neuroscience, 13. ISSN 1662-5102
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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.
Item Type: | Article |
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Subjects: | Librbary Digital > Medical Science |
Depositing User: | Unnamed user with email support@librbarydigit.com |
Date Deposited: | 27 May 2023 06:22 |
Last Modified: | 26 Jul 2024 07:19 |
URI: | http://info.openarchivelibrary.com/id/eprint/782 |