Early Communication Deficits in the Shank1 Knockout Mouse Model for Autism Spectrum Disorder: Developmental Aspects and Effects of Social Context
Early Communication Deficits in the Shank1 Knockout Mouse Model for Autism Spectrum Disorder: Developmental Aspects and Effects of Social Context
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DOI：
10.1002/aur.1564
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发表时间：
2016-06-01
期刊：
影响因子：
4.7
通讯作者：
Woehr, Markus
中科院分区：
文献类型：
--
作者：
Sungur, A. Oezge;Schwarting, Rainer K. W.;Woehr, Markus
SHANK基因的改变在自闭症谱系障碍（ASD）中被反复报道。ASD是一组神经发育障碍，诊断为在多个环境中持续缺乏社交/互动，具有受限/重复的行为模式。迄今为止，ASD的诊断标准纯粹是行为学定义的，可靠的生物标志物尚未确定。因此，ASD小鼠模型的有效性强烈依赖于其行为表型。在这里，我们通过比较Shank 1（-/-）无效突变体，Shank 1（+/-）杂合子和Shank 1（+/+）野生型同窝对照，在ASD的Shank 1小鼠模型中研究了通过隔离诱导的幼崽超声发声（USV）进行的通信。本研究的第一个目的是评估Shank 1基因缺失对沟通发展方面的影响，以了解ASD相关的沟通缺陷是否是由于一般性障碍或发展延迟。其次，我们关注社会背景对USV生产的影响。我们发现，Shank 1（-/-）幼崽发声较少，并显示出典型的倒U形发育USV发射模式的延迟，USV率在出生后第9天（PND）达到峰值，导致PND 6的显著基因型差异。此外，在社会条件下进行的测试显示，无论对社会背景的熟悉程度如何，基因型依赖性缺陷都更加突出。由于沟通的定义是一种社会功能，因此将社会成分引入到典型的非社会测试环境中可能有助于揭示ASD小鼠模型中的沟通缺陷。总之，这些结果表明，SHANK 1参与了跨物种的声音交流，SHANK 1的遗传改变导致了社会交流/互动的缺陷。(C)2015年国际自闭症研究学会，Wiley Periodicals，Inc。
Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation-induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1(-/-) null mutant, Shank1(+/-) heterozygous, and Shank1(+/+) wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD-related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1(-/-) pups vocalized less and displayed a delay in the typical inverted U-shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype-dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. (C) 2015 International Society for Autism Research, Wiley Periodicals, Inc.