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Letting a Typical Mouse Judge Whether Mouse Social Interactions Are Atypical

Thursday, 2 May 2013: 09:00-13:00
Banquet Hall (Kursaal Centre)
C. R. Shah1 and J. Veenstra-VanderWeele2, (1)Vanderbilt University, Nashville, TN, (2)Monroe Carell Children's Hospital at Vanderbilt University, Nashville, TN
Background: Diagnosis of an autism spectrum disorder (ASD) requires a qualitative assessment of social aptitude: one person judging whether another person interacts in a ‘typical’ way.  Thus far, quantitative assessment of behavior has not been used in diagnosis of autism.  In contrast, genetic or behavioral mouse models of autism are typically evaluated by quantification of social behavior, either by time spent in proximity to another mouse or by particular behaviors exhibited during direct social interactions.

Objectives: Rather than quantifying mouse behavior during social interactions, we hypothesized that a typical mouse could be used to make a judgment of another mouse's social behavior. We used a three-chamber paradigm to ask whether typical mouse 'judges' prefer ‘typical’ over ‘atypical’ social interactions with mouse models relevant to ASD. 

Methods: We used wildtype C57BL/6 (B6) mice as ‘judges’ and evaluated their preference for a chamber containing a ‘typical’ (B6 or 129S6) or an ‘atypical’ mouse. For our atypical mouse stimuli, we chose two inbred strains with well-documented social phenotypes (BTBR and BALB/c), as well a mutant line with abnormal social behavior and seizures (Gabrb3 +/-). 

Results: Overall, we observed a stimulus by time interaction (P < 0.0001), with B6 mice preferring the typical mouse chamber during the last 10 minutes of the 30-minute test. For two of the individual stimulus pairings, we observed a similar chamber by time interaction (BALB/c vs. 129S6, P = 0.0007; Gabrb3 +/- vs. 129S6, P = 0.033). For the third stimulus pairing, we found a trend for preference of the typical mouse across time (BTBR vs. B6, P = 0.051). We repeated the experiments using 129S6 mice as judges and found a significant overall interaction (P = 0.034), but only one stimulus pairing reached significance on its own (BALB/c vs. 129S6, P = 0.0021). 

Conclusions: These data suggest that a characteristic pattern of exploration in B6 mice can distinguish some socially atypical animals from controls.  These data need to be replicated across laboratories to evaluate whether mouse preference for typical social interactions may be useful to evaluate social competence in mouse models relevant to autism spectrum disorders.

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