Behavioral Characterization of Shank3B Mice Across Both Sexes

Research Background

Autism Spectrum Disorder (ASD) is a group of complex mental disorders characterized by abnormalities in social interaction and repetitive behaviors. The Shank3B mutant ASD mouse model is widely used in research; however, the behavioral phenotype of this model has not been fully elucidated. This study used a three-dimensional motion capture system and linear discriminant analysis to comprehensively record and analyze the behavioral patterns of male and female Shank3B mutant mice. The study found that both sexes replicated the core and accompanying symptoms of ASD, with significant gender differences. Additionally, Shank3B heterozygous knockout mice exhibited autistic behaviors distinctly different from wild-type and homozygous knockout mice. These findings support the inclusion of both sexes in autism research and the use of experimental methods to efficiently characterize clinically relevant heterozygous transgenic models.

Paper Source

This research was conducted by Liu Jingjing, Ye Jialin, Ji Chunyuan, Ren Wenying, He Youwei, Xu Fuqiang, Wang Feng, et al., and is published in Neuroscience Bulletin (Neurosci. Bull.). The paper was accepted and published on November 20, 2023. The authors are affiliated with the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions; and the University of Chinese Academy of Sciences.

Research Details

Experimental Procedure

The experiment included 114 Shank3B heterozygous knockout, homozygous knockout, and corresponding wild-type mice aged 12-16 weeks. A three-dimensional motion capture system was used to collect spontaneous behavior data from the mice. By tracking 16 key body parts, the mice’s skeletons were reconstructed, and 40 behavioral actions were identified using unsupervised clustering methods. Through behavioral mapping analysis tools, these behavioral actions were further refined into 13 major behavioral movements, corresponding to 5 behavioral clusters.

Research Results

The study found that Shank3B mutant mice of different genotypes exhibited different spontaneous behavioral characteristics between the two sexes. KO (knockout) mice showed significantly reduced walking, jumping, and other movements in both sexes, and increased grooming behavior (representing stereotypical actions in ASD). Heterozygous mice showed different behavioral characteristics from KO mice in both sexes, displaying significantly increased grooming and decreased movement. The analysis also indicated that gender differences were present across different genotype mice, with the most significant differences observed in WT (wild-type) mice.

Conclusions and Significance

The research results indicate that including both male and female mice in the study not only provides more comprehensive behavioral data for Shank3B mutant mice but may also improve the translational efficiency of ASD research. This study will aid in understanding the correlation between genotype and phenotype, and in discovering the neuropathological mechanisms in different sexes in ASD animal models, which will contribute to a deeper understanding of the pathological mechanisms in patients with Shank3B-related ASD.

Research Highlights

• The introduction of a three-dimensional motion capture system allows researchers to capture a wider spectrum of behavioral actions in mice.
• The study includes Shank3B mice of both sexes, helping to more comprehensively understand the impact of gender on ASD behavioral characteristics.
• The inclusion of heterozygous mice makes the experimental model closer to clinical ASD cases, enhancing the clinical relevance of the research.