Behavioral Characterization of Heterogeneous Shank3 Homer Binding Domain Deletion Model of Autism

Thursday, May 17, 2012
Sheraton Hall (Sheraton Centre Toronto)
10:00 AM

ABSTRACT WITHDRAWN

Background: Autism spectrum disorders (ASDs) are common, debilitating disorders affecting social interaction, communication, and repetitive behaviors.  Deletion and other loss-of-function mutations of shank3, an indirect binding partner of neuroligins, have been strongly implicated in autism.

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.

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