UC San Diego

The segment polarity protein Dishevelled-2 (Dvl2) is a component of the Dishevelled protein family that plays an important role in the Wnt developmental signal transduction pathways expressed within the central nervous system. It has an antagonistic function to other Dishevelled proteins in facilitating endocytosis of Frizzled3 Wnt receptors, though the specific behavioral effects have yet to be properly elucidated. A recently described genomic disorder characterized by a microdeletion of the 17p13.1 region, which contains an overlapping region with Dvl2, correlated to a recognizable phenotype in human patients consisting of intellectual disability and delay in social interaction. We sought to utilize various behavioral assays to test several behaviors associated with these phenotypes in adult mice lacking Dvl2 to demonstrate if the disruptions of neural development can be replicated in rodents and to potentially implicate Dvl2 knockout with these developmental delays. The behavioral paradigms used include open field, novel object recognition, and three-chamber social interaction tests to assess locomotor activity, anxiety-like behavior, learning and memory, sociability, and social novelty. An exploratory drive towards the center of a new environment as well as less preference for novel objects in contrast to familiar ones was observed in Dvl2-deficient mice, revealing a noticeable impairment in anxiety-like behavior and in context-independent memory. Impairments in sociability and social novelty were also observed, though without completely removing functionality. Therefore, evidence is provided that a lack of Dvl2 is associated with anxiety, memory, and social behavior deficits.