Social behavior in 16p11.2 and 22q11.2 copy number variations: Insights from mice and humans

Abstract

Genetic 16p11.2 and 22q11.2 deletions and duplications in humans may alter behavioral developmental trajectories increasing the risk of autism and schizophrenia spectrum disorders, and of attention‐deficit/hyperactivity disorder. In this review, we will concentrate on 16p11.2 and 22q11.2 deletions' effects on social functioning, beyond diagnostic categorization. We highlight diagnostic and social sub‐constructs discrepancies. Notably, we contrast evidence from human studies with social profiling performed in several mouse models mimicking 16p11.2 and 22q11.2 deletion syndromes. Given the complexity of social behavior, there is a need to assess distinct social processes. This will be important to better understand the biology underlying such genetic‐dependent dysfunctions, as well as to give perspective on how therapeutic strategies can be improved. Bridges and divergent points between human and mouse studies are highlighted. Overall, we give challenges and future perspectives to sort the genetics of social heterogeneity.

Changes in social behaviour with alterations of MAPK3 and KCTD13/CUL3 pathways in two new outbred rat models for the 16p11.2 syndromes with autism spectrum disorders

“…Considering this reciprocal impact on BMI and head size, it has been suggested that changes in gene transcript levels could be responsible for the symptoms associated with these CNVs. More importantly, the severity of the developmental delay and other comorbidities vary significantly in the human population with some people having an ASD or IQ below 70 and others just below average [21][22][23].…”

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

“…Sensory abilities were minimally affected, except in one model that appeared to be deaf due certainly to the genetic background (6,22). Over the different models, the variability of the social deficit attracted attention (18). One potential confounding factor is the genetic background of the models.…”

“…Patients may also present atypical brain anatomy, with abnormalities in the cerebellar tonsil (16), auditory and speech pathways, as well as in the cortical and striatal structures (17). Overall, these patients frequently display social interaction and communication impairments, especially in speech development (18). They also show poorer adaptative abilities in their daily life compared to controls (13).…”

From basic social neurobiology to better understanding of neurodevelopmental disorders

“…The special issue is concluded with two important reviews on neurodevelopmental disorders and their animal models. The review by Benedetti and colleagues takes on one genetic mechanism with high penetrance for such disorders 20 . Namely, authors screened over 750 publications and analyzed 58 studies in humans and 16 studies in mice that focused on behavioral characterization of subjects with copy number variations (CNVs) in DNA segments 16p11.2 and 22q11.2.…”

“…The review by Benedetti and colleagues takes on one genetic mechanism with high penetrance for such disorders. 20 Namely, authors screened over 750 publications and analyzed 58 studies in humans and 16 studies in mice that focused on behavioral characterization of subjects with copy number variations (CNVs) in DNA segments 16p11.2 and 22q11.2. CNVs on these genetic loci are associated with substantially increased risk for ASD, schizophrenia and attention deficit disorder.…”