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Publication : Systematic autistic-like behavioral phenotyping of 4 mouse strains using a novel wheel-running assay.

First Author  Karvat G Year  2012
Journal  Behav Brain Res Volume  233
Issue  2 Pages  405-14
PubMed ID  22633921 Mgi Jnum  J:190481
Mgi Id  MGI:5448910 Doi  10.1016/j.bbr.2012.05.028
Citation  Karvat G, et al. (2012) Systematic autistic-like behavioral phenotyping of 4 mouse strains using a novel wheel-running assay. Behav Brain Res 233(2):405-14
abstractText  Three core symptoms of autistic spectrum disorders are stereotypic movements, resistance to change in routines and deficits in social interaction. In order to understand their neuronal mechanisms, there is a dire need for behavioral paradigms to assess those symptoms in rodents. Here we present a novel method which is based on positive reward in a customized wheel-running apparatus to assess these symptoms. As a proof of concept, 4 mouse strains were tested in the new behavioral paradigm; 2 control lines (C57BL/6 and ICR) and 2 mouse-models of autism (BTBR T+ tf/J and Nlgn3(tm1Sud)). We found that the C57BL/6, ICR and Nlgn3(tm1Sud) mice showed a significant reduction in stereotypical behavior in the presence of the running wheel, ability to forfeit the running habit when the running-wheel was jammed, and preference of interacting with a social stimulus over the jammed running-wheel. No difference was found between genotypes of the Nlgn3(tm1Sud) mice. On the other hand, the BTBR mice exhibited persistent, elevated levels of stereotypical behavior. In addition, they presented a deficit in their ability to adjust to a changing environment, as manifested in persistence to interact with the wheel even when it was jammed. Lastly, the BTBR mice exhibited no significant preference to interact with the stranger mouse over the jammed running-wheel. These results were validated by a set of commonly used behavioral tests. Overall, our novel behavioral paradigm detects multiple components of autistic-like phenotypes, including cognitive rigidity, stereotypic behavior and social deficiency.
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