当前位置: X-MOL 学术Mol. Autism › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Differentially altered social dominance- and cooperative-like behaviors in Shank2- and Shank3-mutant mice
Molecular Autism ( IF 6.2 ) Pub Date : 2020-10-30 , DOI: 10.1186/s13229-020-00392-9
Kyung Ah Han 1 , Taek Han Yoon 1 , Jungsu Shin 1 , Ji Won Um 1, 2 , Jaewon Ko 1
Affiliation  

Recent progress in genomics has contributed to the identification of a large number of autism spectrum disorder (ASD) risk genes, many of which encode synaptic proteins. Our understanding of ASDs has advanced rapidly, partly owing to the development of numerous animal models. Extensive characterizations using a variety of behavioral batteries that analyze social behaviors have shown that a subset of engineered mice that model mutations in genes encoding Shanks, a family of excitatory postsynaptic scaffolding proteins, exhibit autism-like behaviors. Although these behavioral assays have been useful in identifying deficits in simple social behaviors, alterations in complex social behaviors remain largely untested. Two syndromic ASD mouse models—Shank2 constitutive knockout [KO] mice and Shank3 constitutive KO mice—were examined for alterations in social dominance and social cooperative behaviors using tube tests and automated cooperation tests. Upon naïve and salient behavioral experience, expression levels of c-Fos were analyzed as a proxy for neural activity across diverse brain areas, including the medial prefrontal cortex (mPFC) and a number of subcortical structures. As previously reported, Shank2 KO mice showed deficits in sociability, with intact social recognition memory, whereas Shank3 KO mice displayed no overt phenotypes. Strikingly, the two Shank KO mouse models exhibited diametrically opposed alterations in social dominance and cooperative behaviors. After a specific social behavioral experience, Shank mutant mice exhibited distinct changes in number of c-Fos+ neurons in the number of cortical and subcortical brain regions. Our results underscore the heterogeneity of social behavioral alterations in different ASD mouse models and highlight the utility of testing complex social behaviors in validating neurodevelopmental and neuropsychiatric disorder models. In addition, neural activities at distinct brain regions are likely collectively involved in eliciting complex social behaviors, which are differentially altered in ASD mouse models.

中文翻译:

Shank2 和 Shank3 突变小鼠的社会优势和合作行为的差异改变

基因组学的最新进展有助于识别大量自闭症谱系障碍 (ASD) 风险基因,其中许多基因编码突触蛋白。我们对 ASD 的理解进展迅速,部分原因是开发了许多动物模型。使用分析社会行为的各种行为电池进行的广泛表征表明,模拟编码 Shanks(兴奋性突触后支架蛋白家族)基因突变的一部分工程小鼠表现出类似自闭症的行为。尽管这些行为分析在识别简单社会行为的缺陷方面很有用,但复杂社会行为的改变在很大程度上仍未得到检验。使用试管测试和自动合作测试检查了两种综合征 ASD 小鼠模型——Shank2 组成型敲除 [KO] 小鼠和 Shank3 组成型 KO 小鼠的社会优势和社会合作行为的变化。根据天真和显着的行为经验,c-Fos 的表达水平被分析作为不同大脑区域神经活动的代表,包括内侧前额叶皮层 (mPFC) 和许多皮层下结构。正如之前报道的那样,Shank2 KO 小鼠表现出社交能力缺陷,具有完整的社会识别记忆,而 Shank3 KO 小鼠没有表现出明显的表型。引人注目的是,两个 Shank KO 小鼠模型在社会支配地位和合作行为方面表现出截然相反的变化。在特定的社会行为体验之后,Shank 突变小鼠在皮质和皮质下大脑区域的数量中表现出 c-Fos+ 神经元数量的明显变化。我们的结果强调了不同 ASD 小鼠模型中社会行为改变的异质性,并强调了测试复杂社会行为在验证神经发育和神经精神疾病模型中的效用。此外,不同大脑区域的神经活动可能共同参与引发复杂的社会行为,这些行为在 ASD 小鼠模型中发生了不同的改变。我们的结果强调了不同 ASD 小鼠模型中社会行为改变的异质性,并强调了测试复杂社会行为在验证神经发育和神经精神疾病模型中的效用。此外,不同大脑区域的神经活动可能共同参与引发复杂的社会行为,这些行为在 ASD 小鼠模型中发生了不同的改变。我们的结果强调了不同 ASD 小鼠模型中社会行为改变的异质性,并强调了测试复杂社会行为在验证神经发育和神经精神疾病模型中的效用。此外,不同大脑区域的神经活动可能共同参与引发复杂的社会行为,这些行为在 ASD 小鼠模型中发生了不同的改变。
更新日期:2020-11-02
down
wechat
bug