International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Nadler JJ, Moy SS, Zou F, Wright FA, Crawley JN, Threadgill DW, Magnuson TR

1 University of North Carolina, Chapel Hill, United States, 2 National Institute of Mental Health, Bethesda, United States

Autism is a uniquely human disorder comprised of three major behavioral components:  social deficits, repetitive/ritualistic behavior and communication abnormalities.  There is a wide range of severity observed in autistic patients as well as the milder, non-clinical manifestation of the Broader Autism Phenotype (BAP) in family members.  Just as humans can span the range of autistic to BAP to reserved to outgoing, various inbred lines of mice exhibit a range of different behaviors. 

We are correlating molecular profiling with social behaviors and cognitive flexibility of a variety of inbred strains in order to begin to dissect the complex trait of autism.  Data on social behavior are being collected using a three-chambered apparatus containing an unfamiliar mouse in a wire cage on one side, an empty wire cage on the other and a clear middle chamber.  Several measurements are taken over the ten-minute task, including time spent in each chamber, number of entries into each chamber and sniffing directed at the wire cages.  A second ten-minute task involved placing another unfamiliar mouse in the previously empty wire cage to assess preference for the novel mouse over the now-familiar mouse.  Cognitive flexibility is being measured through training and reversal on a t-maze.  Animals are trained to find a food reward in one arm of a t-shaped maze.  Upon reaching criterion, the food reward is switched to the opposite arm, measuring the animal’s ability to relearn the task in a different way.

We are observing that these behavioral characteristics vary in some strains, indicating a strong genetic component.  In order to profile the expression of genes associated with autism-like behaviors, microarray analyses are being conducted on seven brain regions implicated in autism or social behavior.  Data on strain-dependent gene expression will be presented. In this way we hope to begin to dissect the complex genetics of social behaviors and autism.

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