Early Neurobehavioral Characterization of the CD Mouse Model of Williams-Beuren Syndrome

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomic microdeletion (7q11.23). WBS has been modeled by a mouse line having a complete deletion (CD) of the equivalent mouse locus. This model has been largely used to investigate the etiopathological mechanisms of WBS, although pharmacological therapies have not been identified yet. Surprisingly, CD mice were so far mainly tested in adulthood, despite the developmental nature of WBS and the critical relevance of early timing for potential treatments. Here we provide for the first time a phenotypic characterization of CD mice of both sexes during infancy and adolescence, i.e., between birth and 7 weeks of age. CD pups of both sexes showed reduced body growth, delayed sensory development, and altered patterns of ultrasonic vocalizations and exploratory behaviors. Adolescent CD mice showed reduced locomotion and acoustic startle response, and altered social interaction and communication, the latter being more pronounced in female mice. Juvenile CD mutants of both sexes also displayed reduced brain weight, cortical and hippocampal dendritic length, and spine density. Our findings highlight the critical relevance of early neurobehavioral alterations as biomarkers of WBS pathology, underlying the importance of adolescence for identifying novel therapeutic targets for this neurological disorder.

Automated summary

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by a chromosomal microdeletion (7q11.23). A mouse model with a complete deletion (CD) of the equivalent mouse locus has been used to study the mechanisms of WBS. In this study, CD mice were characterized during infancy and adolescence, and exhibited reduced body growth, delayed sensory development, altered behaviors and neuroanatomical changes. These findings highlight the importance of early neurobehavioral alterations as biomarkers for WBS and the significance of adolescence in identifying potential therapeutic targets.