Genetic-background modulation of core and variable autistic-like symptoms in Fmr1 knock-out mice

Susanna Pietropaolo, Aurélie Guilleminot, Benoît Martin, Francesca R. D'Amato, Wim E. Crusio
PLoS ONE. 2011-02-22; 6(2): e17073
DOI: 10.1371/journal.pone.0017073

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Pietropaolo S(1), Guilleminot A, Martin B, D’Amato FR, Crusio WE.

Author information:
(1)Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, Université
de Bordeaux and CNRS UMR 5287, Talence, France.

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.


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