Gonçalves Ana Margarida, Sousa Nuno, Jacinto Luis, Monteiro Patricia
Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal.
ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Front Behav Neurosci. 2023 Aug 24;17:1205507. doi: 10.3389/fnbeh.2023.1205507. eCollection 2023.
Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, repetitive behaviors, and sensory alterations, with auditory hypersensitivity being one of the most commonly reported sensory-perceptual abnormalities. Several candidate genes for involvement in this disorder have emerged from patient studies, including , a gene that encodes a protein (SHANK3) in the postsynaptic density of excitatory synapses. Previous work has shown that mutant mice carrying a human ASD mutation in the gene () exhibit repetitive behaviors and social interaction deficits, indicating important construct and face validity for this genotype as an animal model of ASD.
To further address whether these mice also present auditory sensory-perceptual alterations, we developed a novel behavioral test in which mice can choose between different soundscapes.
Our results reveal that, in comparison to wild-type mice, mutants display a strong behavioral preference toward silent regions of the arena.
These data suggest that - mutant mice might express an auditory hypersensitivity phenotype, further adding to the face validity of this genotype as an animal model of ASD.
自闭症谱系障碍(ASD)的特征是沟通和社交互动缺陷、兴趣受限、重复行为以及感觉改变,听觉过敏是最常报告的感觉知觉异常之一。患者研究中出现了几个可能参与该疾病的候选基因,包括 ,该基因在兴奋性突触的突触后致密物中编码一种蛋白质(SHANK3)。先前的研究表明,在 基因()中携带人类ASD突变的突变小鼠表现出重复行为和社交互动缺陷,表明这种基因型作为ASD动物模型具有重要的结构效度和表面效度。
为了进一步研究这些小鼠是否也存在听觉感觉知觉改变,我们开发了一种新的行为测试,让小鼠在不同的音景之间进行选择。
我们的结果显示,与野生型小鼠相比, 突变体对竞技场的安静区域表现出强烈的行为偏好。
这些数据表明, 突变小鼠可能表现出听觉过敏表型,进一步增加了这种基因型作为ASD动物模型的表面效度。