Sungur A Özge, Schwarting Rainer K W, Wöhr Markus
Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Gutenbergstr. 18, D-35032, Germany.
Autism Res. 2016 Jun;9(6):696-709. doi: 10.1002/aur.1564. Epub 2015 Sep 30.
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. Autism Res 2016, 9: 696-709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
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，其诊断依据是在多种情境下社交沟通/互动持续存在缺陷，伴有受限/重复的行为模式。迄今为止，ASD的诊断标准完全基于行为定义，尚未确定可靠的生物标志物。因此，ASD小鼠模型的有效性在很大程度上依赖于其行为表型。在此，我们通过比较Shank1基因敲除（Shank1(-/-)）的纯合突变体、Shank1(+/-)杂合子以及Shank1(+/+)野生型同窝对照小鼠，研究了ASD的Shank1小鼠模型中由隔离诱导的幼崽超声波发声（USV）进行的交流。本研究的首要目的是评估Shank1基因缺失对交流发育方面的影响，以确定与ASD相关的交流缺陷是由于一般性功能损害还是发育延迟。其次，我们关注社交情境对USV产生的影响。我们发现，Shank1(-/-)幼崽发声较少，并且在典型的倒U形发育性USV发声模式上出现延迟，USV发生率在出生后第9天（PND9）达到峰值，导致在PND6时出现显著的基因型差异。此外，在社交条件下进行测试发现，无论社交情境的熟悉程度如何，基因型依赖性缺陷都更加明显。由于交流从定义上来说具有社交功能，因此在通常非社交的测试环境中引入社交成分可能有助于揭示ASD小鼠模型中的交流缺陷。总之，这些结果表明SHANK1参与了跨物种的声学交流，SHANK1基因的改变会导致社交沟通/互动缺陷。《自闭症研究》2016年，9: 696 - 709。© 2015国际自闭症研究协会，威利期刊公司
