Jingjing Liu1,2,3,7 · Jialin Ye4,5,6 · Chunyuan Ji4,5,6 · Wenting Ren4,5,6 · Youwei He1,2,3 · Fuqiang Xu1,2,3,7 · Feng Wang1,4,5,61 NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
2 Shenzhen Key Laboratory of Viral Vectors for Biomedicine, Translational Research Center for the Nervous System, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
3 Key Laboratory of Quality Control Technology for Virus-Based Therapeutics, Guangdong Provincial Medical Products Administration, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
4 Shenzhen Key Lab of Translational Research for Brain Diseases, Translational Research Center for the Nervous System, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
5 Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
6 CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
7 University of Chinese Academy of Sciences, Beijing 100049, China
Abstract
Autism spectrum disorders (ASD) are characterized by social and repetitive abnormalities. Although the ASD mouse model with Shank3b mutations is widely used in ASD research, the behavioral phenotype of this model has not been fully elucidated. Here, a 3D-motion capture system and linear discriminant analysis were used to comprehensively record and analyze the behavioral patterns of male and female Shank3b mutant mice. It was found that both sexes replicated the core and accompanied symptoms of ASD, with significant sex differences. Further, Shank3b heterozygous knockout mice exhibited distinct autistic behaviors, that were significantly different from those those observed in the wild type and homozygous knockout groups. Our findings provide evidence for the inclusion of both sexes and experimental approaches to efficiently characterize heterozygous transgenic models, which are more clinically relevant in autistic studies.
Keywords
Autism; Shank3b; Spontaneous behavior; 3D animal motion-capture system; Computational ethology; Sex diferences
