[article] 
inAutism Research > 10-6 (June 2017) . - p.1067-1078

Titre :	Age-specific autistic-like behaviors in heterozygous Fmr1-KO female mice
Type de document :	Texte imprimé et/ou numérique
Auteurs :	Manon GAUDUCHEAU, Auteur ; Valerie LEMAIRE-MAYO, Auteur ; Francesca R. D'AMATO, Auteur ; Diego ODDI, Auteur ; Wim E. CRUSIO, Auteur ; Susanna PIETROPAOLO, Auteur
Article en page(s) :	p.1067-1078
Langues :	Anglais (eng)
Mots-clés :	adolescence  ultrasonic vocalizations  social interactions  developmental disorders  Fragile X syndrome  animal models  autism
Index. décimale :	PER Périodiques
Résumé :	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.
En ligne :	http://dx.doi.org/10.1002/aur.1743
Permalink :	https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=309

[article] Age-specific autistic-like behaviors in heterozygous Fmr1-KO female mice [Texte imprimé et/ou numérique] / Manon GAUDUCHEAU, Auteur ; Valerie LEMAIRE-MAYO, Auteur ; Francesca R. D'AMATO, Auteur ; Diego ODDI, Auteur ; Wim E. CRUSIO, Auteur ; Susanna PIETROPAOLO, Auteur . - p.1067-1078.
Langues : Anglais (eng)
in Autism Research > 10-6 (June 2017) . - p.1067-1078

Mots-clés :	adolescence  ultrasonic vocalizations  social interactions  developmental disorders  Fragile X syndrome  animal models  autism
Index. décimale :	PER Périodiques
Résumé :	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.
En ligne :	http://dx.doi.org/10.1002/aur.1743
Permalink :	https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=309