Genetic-Background Modulation of Core and Variable Autistic-Like Symptoms in Fmr1 Knock-Out Mice

Abstract

BACKGROUND No animal models of autism spectrum disorders (ASD) with good construct validity are currently available; using genetic models of pathologies characterized by ASD-like deficits, but with known causes, may be therefore a promising strategy. The Fmr1-KO mouse is an example of this approach, modeling Fragile X syndrome, a well-known genetic disorder presenting ASD symptoms. The Fmr1-KO is available on different genetic backgrounds (FVB versus C57BL/6), which may explain some of the conflicting results that have been obtained with these mutants up till now. METHODS Fmr1 KO and their wild-type littermates on both the FVB and C57BL/6 genetic backgrounds were examined on a battery of tests modeling the clinical symptoms of ASD, including the triad of core symptoms (alterations in social interaction and communication, presence of repetitive behaviors), as well as the secondary symptoms (disturbances in sensori-motor reactivity and in circadian patterns of activity, epileptic events). RESULTS Fmr1-KO mice displayed autistic-like core symptoms of altered social interaction and occurrence of repetitive behaviors with additional hyperactivity. The genetic background modulated the effects of the Fmr1 deletion and it appears that the C57BL/6 background may be more suitable for further research on core autistic-like symptoms. CONCLUSIONS The Fmr1-mouse line does not recapitulate all of the main core and secondary ASD symptoms, but still can be useful to elucidate the neurobiological mechanisms underlying specific ASD-like endophenotypes.

DOI: 10.1371/journal.pone.0017073

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@inproceedings{Pietropaolo2011GeneticBackgroundMO, title={Genetic-Background Modulation of Core and Variable Autistic-Like Symptoms in Fmr1 Knock-Out Mice}, author={Susanna Pietropaolo and Aur{\'e}lie Guilleminot and Beno{\^i}t Martin and Francesca R D'amato and Wim E Crusio}, booktitle={PloS one}, year={2011} }