Abstract
Background : Calcium/calmodulin-dependent serine protein kinase (CASK) is a synaptic scaffolding protein and mutations in the CASK gene have been identified in various types of neurodevelopmental disorders. Deficit in social behavior is a common symptom of many neurodevelopmental disorders and also accompanies CASK related disorders. The deep layer of the medial prefrontal cortex (mPFC) has been suggested to be responsible for social behavior.
Methods : To study the effect of CASK deficiency on social behavior, we generated mPFC specific CASK knockdown mice by introducing CASK short-hairpin RNA using adeno-associated viral (AAV) injection. We studied the behaviors of CASK knockdown and enhanced green fluorescent protein (EGFP) expressing AAV injected control mice using open field and three-chamber apparatus.
Results : CASK knockdown mice showed normal locomotor activity, anxiety level, and repetitive behavior in the observation in the open field arena, but they showed deficit in reciprocal social interaction with a juvenile mouse. In the three-chamber test, CASK knockdown mice showed more interaction with a novel juvenile mouse than an empty cage at a similar level to control mice, suggesting that social recognition is intact. On the other hand, no significant difference was observed in the interaction between a novel target mouse and a pre-exposed mouse, suggesting that social memory ability was impaired in the CASK knockdown mice.
Conclusion : By using mPFC specific CASK knockdown mice, we found that CASK deficiency in this area affects the social memory ability. Our results provide insights not only into CASK related disorders, but also a wide range of neurodevelopmental disorders associated with social deficits.
