Objectives: We hypothesize that creating an autism-associated genetic mutation of shank3 in a mouse model will lead to autism-relevant behavioral abnormalities.
Methods: We have characterized a novel genetic model of autism based on deletion of exon 21 of shank3 which encodes for the Homer binding domain at the C-terminal (Bangash et al, Cell, 2011).Behavioral testing was performed on littermate, sex-matched progeny from shank3 C-terminal deletion heterozygotes (Shank3+/ΔC). Core domains of autism related behaviors, repetitive, communication, social, and learning and memory were tested.
Results: Shank3 (+/ΔC) female mice show an increase in time spent grooming compared to WT littermate controls which suggests a repetitive behavior phenotype. To examine correlates of communication, we measured ultrasonic vocalizations emitted by males in the presence of free roaming females. Shank3+/ΔC mice show an increase in latency to emit the first USV. Shank3(+/ΔC) mice exhibited normal social behavior compared to WT littermate controls when tested on three different social interaction tasks including social learning, a social interaction task where an inanimate and a social interaction target were presented sequentially, and a social preference task where an inanimate and a social interaction target were presented simultaneously. In addition, Shank3+/ΔC mice showed normal learning and memory in the Morris water maze and the fear conditioning task. These mice also exhibit normal motor coordination when tested on rotorod.
Conclusions: Overall, these data suggest that Shank3 (+/ΔC) mice show a mild autistic behavioral phenotype.