Day-to-day spontaneous social behaviours is quantitatively and qualitatively affected in a 16p11.2 deletion mouse model

Anna Rusu; Claire Chevalier; Fabrice de Chaumont; Valérie Nalesso; Véronique Brault; Yann Hérault; Elodie Ey

doi:10.3389/fnbeh.2023.1294558

Day-to-day spontaneous social behaviours is quantitatively and qualitatively affected in a 16p11.2 deletion mouse model

Front Behav Neurosci. 2023 Dec 19:17:1294558. doi: 10.3389/fnbeh.2023.1294558. eCollection 2023.

Authors

Anna Rusu¹, Claire Chevalier¹, Fabrice de Chaumont², Valérie Nalesso¹, Véronique Brault¹, Yann Hérault^#^{1

2}, Elodie Ey^#¹

Affiliations

¹ Université de Strasbourg, CNRS, INSERM, Institut de Génétique et de Biologie Moléculaire et Cellulaire‑UMR 7104-UMR-S 1258, Illkirch, France.
² Génétique Humaine et Fonctions Cognitives, Institut Pasteur, Université de Paris Cité, Paris, France.

^# Contributed equally.

Abstract

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.

Keywords: 16p11.2 deletion; autism; long-term monitoring; mouse model; social behaviour; spontaneous behaviour; ultrasonic vocalisations.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Centre for Scientific Research (CNRS), the French National Institute of Health and Medical Research (INSERM), the University of Strasbourg (Unistra), the French government funds through the “Agence Nationale de la Recherche” in the framework of the Investissements d’Avenir Program [ANR-10-INBS-07 PHENOMIN to YH] and Investissements d’Avenir labeled IdEx Unistra [ANR-10-IDEX-0002 to YH], a SFRI-STRAT’US project [ANR 20-SFRI-0012 to YH], EUR IMCBio [ANR-17-EURE-0023 to YH], STRAS&ND [to EE and YH], INBS PHENOMIN [ANR-10-INBS-07 PHENOMIN to YH]. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.