Age-specific autistic-like behaviors in heterozygous Fmr1-KO female mice / Manon GAUDUCHEAU in Autism Research, 10-6 (June 2017)  

Public ISBD [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

Autistic-relevant behavioral phenotypes of a mouse model of cyclin-dependent kinase-like 5 deficiency disorder / Oceane COIFFARD ; Celeste FERRAGUTO ; Athanasios MANOLIS ; Elisabetta CIANI ; Susanna PIETROPAOLO in Autism Research, 17-9 (September 2024)  

Public ISBD [article]  inAutism Research > 17-9 (September 2024) . - p.1742-1759 Titre : Autistic-relevant behavioral phenotypes of a mouse model of cyclin-dependent kinase-like 5 deficiency disorder Type de document : Texte imprimé et/ou numérique Auteurs : Oceane COIFFARD, Auteur ; Celeste FERRAGUTO, Auteur ; Athanasios MANOLIS, Auteur ; Elisabetta CIANI, Auteur ; Susanna PIETROPAOLO, Auteur Article en page(s) : p.1742-1759 Langues : Anglais (eng) Mots-clés : acoustic startle  CDD  mouse pups  neurodevelopmental disorders  social behaviors  social interaction  ultrasonic vocalizations Index. décimale : PER Périodiques Résumé : Abstract Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene and characterized by early-onset epilepsy, intellectual disability, and autistic features. To date, the etiological mechanisms underlying CDD are largely unknown and no effective therapies are available. The Cdkl5 knock-out (KO) mouse has been broadly employed in preclinical studies on CDD; Cdkl5-KO mice display neurobehavioral abnormalities recapitulating most CDD symptoms, including alterations in motor, sensory, cognitive, and social abilities. However, most available preclinical studies have been carried out on adult Cdkl5-KO mice, so little is known about the phenotypic characteristics of this model earlier during development. Furthermore, major autistic-relevant phenotypes, for example, social and communication deficits, have been poorly investigated and mostly in male mutants. Here, we assessed the autistic-relevant behavioral phenotypes of Cdkl5-KO mice during the first three post-natal weeks and in adulthood. Males and females were tested, the latter including both heterozygous and homozygous mutants. Cdkl5 mutant pups showed qualitative and quantitative alterations in ultrasonic communication, detected first at 2?weeks of age and confirmed later in adulthood. Increased levels of anxiety-like behaviors were observed in mutants at 3?weeks and in adulthood, when stereotypies, reduced social interaction and memory deficits were also observed. These behavioral effects of the mutation were evident in both sexes, being more marked and varied in homozygous than heterozygous females. These findings provide novel evidence for the autistic-relevant behavioral profile of the Cdkl5 mouse model, thus supporting its use in future preclinical studies investigating CDD pathology and autism spectrum disorders. En ligne : https://doi.org/10.1002/aur.3226 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=535 [article] Autistic-relevant behavioral phenotypes of a mouse model of cyclin-dependent kinase-like 5 deficiency disorder [Texte imprimé et/ou numérique] / Oceane COIFFARD, Auteur ; Celeste FERRAGUTO, Auteur ; Athanasios MANOLIS, Auteur ; Elisabetta CIANI, Auteur ; Susanna PIETROPAOLO, Auteur . - p.1742-1759. Langues : Anglais (eng) in Autism Research > 17-9 (September 2024) . - p.1742-1759 Mots-clés : acoustic startle  CDD  mouse pups  neurodevelopmental disorders  social behaviors  social interaction  ultrasonic vocalizations Index. décimale : PER Périodiques Résumé : Abstract Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) is a neurodevelopmental disease caused by mutations in the X-linked CDKL5 gene and characterized by early-onset epilepsy, intellectual disability, and autistic features. To date, the etiological mechanisms underlying CDD are largely unknown and no effective therapies are available. The Cdkl5 knock-out (KO) mouse has been broadly employed in preclinical studies on CDD; Cdkl5-KO mice display neurobehavioral abnormalities recapitulating most CDD symptoms, including alterations in motor, sensory, cognitive, and social abilities. However, most available preclinical studies have been carried out on adult Cdkl5-KO mice, so little is known about the phenotypic characteristics of this model earlier during development. Furthermore, major autistic-relevant phenotypes, for example, social and communication deficits, have been poorly investigated and mostly in male mutants. Here, we assessed the autistic-relevant behavioral phenotypes of Cdkl5-KO mice during the first three post-natal weeks and in adulthood. Males and females were tested, the latter including both heterozygous and homozygous mutants. Cdkl5 mutant pups showed qualitative and quantitative alterations in ultrasonic communication, detected first at 2?weeks of age and confirmed later in adulthood. Increased levels of anxiety-like behaviors were observed in mutants at 3?weeks and in adulthood, when stereotypies, reduced social interaction and memory deficits were also observed. These behavioral effects of the mutation were evident in both sexes, being more marked and varied in homozygous than heterozygous females. These findings provide novel evidence for the autistic-relevant behavioral profile of the Cdkl5 mouse model, thus supporting its use in future preclinical studies investigating CDD pathology and autism spectrum disorders. En ligne : https://doi.org/10.1002/aur.3226 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=535

Behavioral abnormalities in the Fmr1-KO2 mouse model of fragile X syndrome: The relevance of early life phases / Julie GAUDISSARD in Autism Research, 10-10 (October 2017)  

Public ISBD [article]  inAutism Research > 10-10 (October 2017) . - p.1584-1596 Titre : Behavioral abnormalities in the Fmr1-KO2 mouse model of fragile X syndrome: The relevance of early life phases Type de document : Texte imprimé et/ou numérique Auteurs : Julie GAUDISSARD, Auteur ; Melanie GINGER, Auteur ; Marika PREMOLI, Auteur ; Maurizio MEMO, Auteur ; Andreas FRICK, Auteur ; Susanna PIETROPAOLO, Auteur Article en page(s) : p.1584-1596 Langues : Anglais (eng) Mots-clés : Fragile X syndrome  autism  development  adolescence  social interaction  anxiety  cognition Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is a developmental disorder caused by a mutation in the X-linked FMR1 gene, coding for the FMRP protein which is largely involved in synaptic function. FXS patients present several behavioral abnormalities, including hyperactivity, anxiety, sensory hyper-responsiveness, and cognitive deficits. Autistic symptoms, e.g., altered social interaction and communication, are also often observed: FXS is indeed the most common monogenic cause of autism. Mouse models of FXS are therefore of great interest for research on both FXS and autistic pathologies. The Fmr1-KO2 mouse line is the most recent FXS model, widely used for brain studies; surprisingly, little is known about the face validity of this model, i.e., its FXS-like behavioral phenotype. Furthermore, no data are available for the age-related expression of the pathological phenotypes in this mouse line, a critical issue for modelling neurodevelopmental disorders. Here we performed an extensive behavioral characterization of the KO2 model at infancy, adolescent and adult ages. Hyperactivity, altered emotionality, sensory hyper-responsiveness and memory deficits were already present in KO mice at adolescence and remained evident at adulthood. Alterations in social behaviors were instead observed only in young KO animals: during the first 2 weeks of life, KOs emitted longer ultrasonic vocalizations compared to their WT littermates and as adolescents they displayed more aggressive behaviors towards a conspecific. These results strongly support the face validity of the KO2 mouse as a model for FXS, at the same time demonstrating that its ability to recapitulate social autistic-relevant phenotypes depends on early testing ages. Autism Res 2017, 10: 1584–1596. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1814 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=322 [article] Behavioral abnormalities in the Fmr1-KO2 mouse model of fragile X syndrome: The relevance of early life phases [Texte imprimé et/ou numérique] / Julie GAUDISSARD, Auteur ; Melanie GINGER, Auteur ; Marika PREMOLI, Auteur ; Maurizio MEMO, Auteur ; Andreas FRICK, Auteur ; Susanna PIETROPAOLO, Auteur . - p.1584-1596. Langues : Anglais (eng) in Autism Research > 10-10 (October 2017) . - p.1584-1596 Mots-clés : Fragile X syndrome  autism  development  adolescence  social interaction  anxiety  cognition Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is a developmental disorder caused by a mutation in the X-linked FMR1 gene, coding for the FMRP protein which is largely involved in synaptic function. FXS patients present several behavioral abnormalities, including hyperactivity, anxiety, sensory hyper-responsiveness, and cognitive deficits. Autistic symptoms, e.g., altered social interaction and communication, are also often observed: FXS is indeed the most common monogenic cause of autism. Mouse models of FXS are therefore of great interest for research on both FXS and autistic pathologies. The Fmr1-KO2 mouse line is the most recent FXS model, widely used for brain studies; surprisingly, little is known about the face validity of this model, i.e., its FXS-like behavioral phenotype. Furthermore, no data are available for the age-related expression of the pathological phenotypes in this mouse line, a critical issue for modelling neurodevelopmental disorders. Here we performed an extensive behavioral characterization of the KO2 model at infancy, adolescent and adult ages. Hyperactivity, altered emotionality, sensory hyper-responsiveness and memory deficits were already present in KO mice at adolescence and remained evident at adulthood. Alterations in social behaviors were instead observed only in young KO animals: during the first 2 weeks of life, KOs emitted longer ultrasonic vocalizations compared to their WT littermates and as adolescents they displayed more aggressive behaviors towards a conspecific. These results strongly support the face validity of the KO2 mouse as a model for FXS, at the same time demonstrating that its ability to recapitulate social autistic-relevant phenotypes depends on early testing ages. Autism Res 2017, 10: 1584–1596. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1814 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=322

---

1 (1 - 3 / 3)