Developmental social communication deficits in the Shank3 rat model of phelan-mcdermid syndrome and autism spectrum disorder.
Developmental social communication deficits in the Shank3 rat model of phelan-mcdermid syndrome and autism spectrum disorder.
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DOI：
10.1002/aur.1925
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Silverman JL
中科院分区：
文献类型：
--
作者：
Berg EL;Copping NA;Rivera JK;Pride MC;Careaga M;Bauman MD;Berman RF;Lein PJ;Harony-Nicolas H;Buxbaum JD;Ellegood J;Lerch JP;Wöhr M;Silverman JL
在自闭症谱系障碍(ASD)和智力残疾费兰-麦克德米德综合征(PMS)中发现了SHANK3基因突变。这项研究利用了一种新的Shank3缺乏症大鼠模型来评估复杂的行为现象，这是大鼠独有的，表现出比小鼠更丰富的社会行为。大鼠独特的可检测到的超声波发声(USV)信号作为情境相关的情感信号，完成重要的交流功能。我们首次报道了幼年Shank3大鼠双向社会交流的叫声和响应声回放分析。有趣的是，我们发现Shank3缺陷的男性并没有表现出在回放亲社会的USV后表现出的增强的社交行为。同时，我们发现USV对回放的反应并不依赖于基因型，并且发出的反应叫声在意义上是不同的。这是利用ASD的遗传模型对这些社会相关反应的第一次报道。一项对青少年互惠社会互动中积极游戏的全面和实证分析进一步表明，通过减少肛门嗅探、跟随/追逐和异体打扮等多个关键参数，儿童玩耍的次数更少，游戏持续时间减少。我们进一步发现，与Shank3野生型对照相比，Shank3基因缺失的雄性幼崽发射的隔离诱导的USV更少。出生后全脑解剖表型被应用于可视化基础上的发育表型。这里提供的数据支持了Shank3在社会交流中的重要作用，社交交流是ASD的核心症状域。通过增加体内功能结果指标的数量，我们增加了识别和推进医疗干预的可能性。
Mutations in the SHANK3 gene have been discovered in autism spectrum disorders (ASD), and the intellectual disability, Phelan-McDermid Syndrome (PMS). This study leveraged a new rat model of Shank3 deficiency to assess complex behavioral phenomena, unique to rats, which display a richer social behavior repertoire than mice. Uniquely detectable emissions of ultrasonic vocalizations (USV) in rats serve as situation-dependent affective signals and accomplish important communicative functions. We report, for the first time, a call and response acoustic playback assay of bidirectional social communication in juvenile Shank3 rats. Interestingly, we found that Shank3-deficient males did not demonstrate the enhanced social approach behavior typically exhibited following playback of pro-social USV. Concomitantly, we discovered that emission of USV in response to playback was not genotype-dependent and emitted response calls were divergent in meaning. This is the first report of these socially relevant responses using a genetic model of ASD. A comprehensive and empirical analysis of vigorous play during juvenile reciprocal social interactions further revealed fewer bouts and reduced durations of time spent playing by multiple key parameters, including reduced anogenital sniffing, following/chasing, and allogrooming. We further discovered that male Shank3-deficient pups emitted fewer isolation-induced USV than Shank3 wildtype controls. Postnatal whole brain anatomical phenotyping was applied to visualize anatomical substrates that underlie developmental phenotypes. The data presented here lend support for the important role of Shank3 in social communication, the core symptom domain of ASD. By increasing the number of in vivo functional outcome measures, we increased the likelihood for identifying and moving forward with medical interventions.
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影响因子：
30.8
作者：
Durand, Christelle M.;Betancur, Catalina;Bourgeron, Thomas
通讯作者：
Bourgeron, Thomas
影响因子：
6.2
作者：
Bozdagi O;Sakurai T;Papapetrou D;Wang X;Dickstein DL;Takahashi N;Kajiwara Y;Yang M;Katz AM;Scattoni ML;Harris MJ;Saxena R;Silverman JL;Crawley JN;Zhou Q;Hof PR;Buxbaum JD
通讯作者：
Buxbaum JD
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影响因子：
11
作者：
Ellegood, J.;Anagnostou, E.;Babineau, B. A.;Crawley, J. N.;Lin, L.;Genestine, M.;DiCicco-Bloom, E.;Lai, J. K. Y.;Foster, J. A.;Penagarikano, O.;Geschwind, D. H.;Pacey, L. K.;Hampson, D. R.;Laliberte, C. L.;Mills, A. A.;Tam, E.;Osborne, L. R.;Kouser, M.;Espinosa-Becerra, F.;Xuan, Z.;Powell, C. M.;Raznahan, A.;Robins, D. M.;Nakai, N.;Nakatani, J.;Takumi, T.;van Eede, M. C.;Kerr, T. M.;Muller, C.;Blakely, R. D.;Veenstra-VanderWeele, J.;Henkelman, R. M.;Lerch, J. P.
通讯作者：
Lerch, J. P.
影响因子：
2.6
作者：
Brudzynski, SM
通讯作者：
Brudzynski, SM
影响因子：
4.7
作者：
Engineer, Crystal T.;Rahebi, Kimiya C.;Kilgard, Michael P.
通讯作者：
Kilgard, Michael P.