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Updated: Jul 6, 2025

Assessing Social Dominance in Mouse Models Using the Tube Test
Published on: June 6, 2025
Day-to-day spontaneous social behaviours is quantitatively and qualitatively affected in a 16p11.2 deletion mouse
Anna Rusu1, Claire Chevalier1, Fabrice de Chaumont2
1Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire‑UMR 7104-UMR-S 1258, Illkirch, France.
Background:
Autism spectrum disorders affect more than 1% of the population, impairing social communication and increasing stereotyped behaviours. A micro-deletion of the 16p11.2 BP4-BP5 chromosomic region has been identified in 1% of patients also displaying intellectual disabilities. In mouse models generated to understand the mechanisms of this deletion, learning and memory deficits were pervasive in most genetic backgrounds, while social communication deficits were only detected in some models.
Methods:
To complement previous studies, we itemized the social deficits in the mouse model of 16p11.2 deletion on a hybrid C57BL/6N × C3H.Pde6b+ genetic background. We examined whether behavioural deficits were visible over long-term observation periods lasting several days and nights, to parallel everyday-life assessment of patients. We recorded the individual and social behaviours of mice carrying a heterozygous deletion of the homologous 16p11.2 chromosomic region (hereafter Del/+) and their wild-type littermates from both sexes over two or three consecutive nights during social interactions of familiar mixed-genotype quartets of males and of females, and of same-genotype unfamiliar female pairs.
Results:
We observed that Del/+ mice of both sexes increased significantly their locomotor activity compared to wild-type littermates. In the social domain, Del/+ mice of both sexes displayed widespread deficits, even more so in males than in females in quartets of familiar individuals. In pairs, significant perturbations of the organisation of the social communication and behaviours appeared in Del/+ females.
Discussion:
Altogether, this suggests that, over long recording periods, the phenotype of the 16p11.2 Del/+ mice was differently affected in the locomotor activity and the social domains and between the two sexes. These findings confirm the importance of testing models in long-term conditions to provide a comprehensive view of their phenotype that will refine the study of cellular and molecular mechanisms and complement pre-clinical targeted therapeutic trials.
Insights
This study reveals that mice with a 16p11.2 deletion exhibit altered social behaviors and increased activity, with sex-specific differences observed over long-term monitoring. These findings highlight the importance of extended observation for understanding autism spectrum disorder models.
Area of Science:
- Neuroscience
- Genetics
- Behavioral Science
Background:
- Autism spectrum disorders (ASD) affect social communication and increase stereotyped behaviors.
- A 16p11.2 micro-deletion is linked to intellectual disabilities and, in mouse models, learning and memory deficits, with variable social communication impairments.
- Previous studies showed mixed results for social deficits in 16p11.2 deletion mouse models.
Purpose of the Study:
- To investigate social deficits in a 16p11.2 deletion mouse model over extended observation periods.
- To assess if behavioral deficits are evident during long-term monitoring, mimicking real-life patient assessment.
- To analyze sex-specific behavioral differences in mice with the 16p11.2 deletion.
Main Methods:
- Utilized a mouse model with a heterozygous deletion of the 16p11.2 region (Del/+).
- Recorded individual and social behaviors over multiple consecutive nights in familiar mixed-genotype quartets and unfamiliar female pairs.
- Compared Del/+ mice with their wild-type littermates, analyzing both sexes.
Main Results:
- Del/+ mice of both sexes showed significantly increased locomotor activity compared to wild-type littermates.
- Widespread social deficits were observed in Del/+ mice of both sexes, more pronounced in males within quartets.
- Significant disruptions in social communication and behavior organization were noted in Del/+ females during pair interactions.
Conclusions:
- Long-term recording reveals sex-specific alterations in locomotor activity and social behavior in the 16p11.2 deletion mouse model.
- Extended observation periods are crucial for a comprehensive phenotype assessment in genetic models of neurodevelopmental disorders.
- Findings support refining studies on cellular/molecular mechanisms and complement pre-clinical therapeutic trials for conditions like ASD.

