Age-specific autistic-like behaviors in heterozygous Fmr1-KO female mice.

Manon Gauducheau, Valerie Lemaire-Mayo, Francesca R. D'Amato, Diego Oddi, Wim E. Crusio, Susanna Pietropaolo
Autism Research. 2017-03-16; 10(6): 1067-1078
DOI: 10.1002/aur.1743

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Gauducheau M(1)(2), Lemaire-Mayo V(1)(2), D’Amato FR(3), Oddi D(3), Crusio WE(1)(2), Pietropaolo S(1)(2).

Author information:
(1)Univ. Bordeaux, INCIA, Pessac cedex, France.
(2)CNRS, INCIA, UMR 5287, Pessac cedex, France.
(3)CNR, Cell Biology and Neurobiology Institute, IRCCS, Santa Lucia Foundation, Rome, Italy.

Fragile X syndrome (FXS) is a major developmental disorder and the most frequent
monogenic cause of autism. Surprisingly, most existing studies on the Fmr1-KO
mouse model for FXS have focused on males, although FX women, who are mostly
heterozygous for the Fmr1 mutation, are known to exhibit several behavioral
deficits, including autistic-like features. Furthermore, most animal research has
been carried out on adults only; so that little is known about the age
progression of the behavioral phenotype of Fmr1 mutants, which is a crucial issue
to optimize the impact of therapeutic interventions. Here, we performed an
extensive analysis of autistic-like social behaviors in heterozygous (HET)
Fmr1-KO females and their WT littermates at different ages. No behavioral
difference between HET and WT mice was observed at infancy, but some
abnormalities in social interaction and communication were first detected at
juvenile age. At adulthood some of these alterations disappeared, but avoidance
of social novelty appeared, together with other FXS-relevant behavioral deficits,
such as hyperactivity and reduced contextual fear response. Our data provide for
the first time evidence for the presence of autistic-relevant behavioral
abnormalities in Fmr1-HET female mice, demonstrating the utility of this mouse
line to model autistic-like behaviors in both sexes. These results also highlight
the importance of taking into account age differences when using the Fmr1-KO
mouse model, suggesting that the early post-natal phases are the most promising
target for preventive interventions and the adult age is the most appropriate to
investigate the behavioral impact of potential therapies. Autism Res 2017. © 2017
International Society for Autism Research, Wiley Periodicals, Inc. Autism Res
2017, 10: 1067-1078. © 2017 International Society for Autism Research, Wiley
Periodicals, Inc.


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