title: Age-specific autistic-like behaviors in heterozygous Fmr1-KO female mice.
abstract: 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.
authors.affiliation: Univ. Bordeaux, INCIA, Pessac cedex, France.|CNRS, INCIA, UMR 5287, Pessac cedex, France.
authors.forename: Manon
authors.initials: M
authors.lastname: Gauducheau
authors.affiliation: Univ. Bordeaux, INCIA, Pessac cedex, France.|CNRS, INCIA, UMR 5287, Pessac cedex, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Lemaire-Mayo
authors.affiliation: CNR, Cell Biology and Neurobiology Institute, IRCCS, Santa Lucia Foundation, Rome, Italy.
authors.forename: Francesca R
authors.initials: FR
authors.lastname: D'Amato
authors.affiliation: CNR, Cell Biology and Neurobiology Institute, IRCCS, Santa Lucia Foundation, Rome, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Oddi
authors.affiliation: Univ. Bordeaux, INCIA, Pessac cedex, France.|CNRS, INCIA, UMR 5287, Pessac cedex, France.
authors.forename: Wim E
authors.initials: WE
authors.lastname: Crusio
authors.affiliation: Univ. Bordeaux, INCIA, Pessac cedex, France.|CNRS, INCIA, UMR 5287, Pessac cedex, France.
authors.forename: Susanna
authors.initials: S
authors.lastname: Pietropaolo
mesh_terms: D000367:Age Factors; D000818:Animals; D001321:Autistic Disorder / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D051379:Mice; D018345:Mice, Knockout; D012919:Social Behavior
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; C497684:Fmr1 protein, mouse
keywords: Fragile X syndrome; adolescence; animal models; autism; developmental disorders; social interactions; ultrasonic vocalizations