2 recherche sur le mot-clé 'CYFIP1'

CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes / Catherine FRICANO-KUGLER in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 25p. Titre : CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes Type de document : texte imprimé Auteurs : Catherine FRICANO-KUGLER, Auteur ; Aaron GORDON, Auteur ; Grace SHIN, Auteur ; Kun GAO, Auteur ; Jenny NGUYEN, Auteur ; Jamee BERG, Auteur ; Mary STARKS, Auteur ; Daniel H. GESCHWIND, Auteur Article en page(s) : 25p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder (ASD)  Cyfip1  Dup15q  Fear conditioning  Mouse behavior  Neurodevelopmental disorders  RNA sequencing Index. décimale : PER Périodiques Résumé : Background: CYFIP1, a protein that interacts with FMRP and regulates protein synthesis and actin dynamics, is overexpressed in Dup15q syndrome as well as autism spectrum disorder (ASD). While CYFIP1 heterozygosity has been rigorously studied due to its loss in 15q11.2 deletion, Prader-Willi and Angelman syndrome, the effects of CYFIP1 overexpression, as is observed in patients with CYFIP1 duplication, are less well understood. Methods: We developed and validated a mouse model of human CYFIP1 overexpression (CYFIP1 OE) using qPCR and western blot analysis. We performed a large battery of behavior testing on these mice, including ultrasonic vocalizations, three-chamber social assay, home-cage behavior, Y-maze, elevated plus maze, open field test, Morris water maze, fear conditioning, prepulse inhibition, and the hot plate assay. We also performed RNA sequencing and analysis on the basolateral amygdala. Results: Extensive behavioral testing in CYFIP1 OE mice reveals no changes in the core behaviors related to ASD: social interactions and repetitive behaviors. However, we did observe mild learning deficits and an exaggerated fear response. Using RNA sequencing of the basolateral amygdala, a region associated with fear response, we observed changes in pathways related to cytoskeletal regulation, oligodendrocytes, and myelination. We also identified GABA-A subunit composition changes in basolateral amygdala neurons, which are essential components of the neural fear conditioning circuit. Conclusion: Overall, this research identifies the behavioral and molecular consequences of CYFIP1 overexpression and how they contribute to the variable phenotype seen in Dup15q syndrome and in ASD patients with excess CYFIP1. En ligne : http://dx.doi.org/10.1186/s13229-019-0278-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402 [article] CYFIP1 overexpression increases fear response in mice but does not affect social or repetitive behavioral phenotypes [texte imprimé] / Catherine FRICANO-KUGLER, Auteur ; Aaron GORDON, Auteur ; Grace SHIN, Auteur ; Kun GAO, Auteur ; Jenny NGUYEN, Auteur ; Jamee BERG, Auteur ; Mary STARKS, Auteur ; Daniel H. GESCHWIND, Auteur . - 25p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 25p. Mots-clés : Autism spectrum disorder (ASD)  Cyfip1  Dup15q  Fear conditioning  Mouse behavior  Neurodevelopmental disorders  RNA sequencing Index. décimale : PER Périodiques Résumé : Background: CYFIP1, a protein that interacts with FMRP and regulates protein synthesis and actin dynamics, is overexpressed in Dup15q syndrome as well as autism spectrum disorder (ASD). While CYFIP1 heterozygosity has been rigorously studied due to its loss in 15q11.2 deletion, Prader-Willi and Angelman syndrome, the effects of CYFIP1 overexpression, as is observed in patients with CYFIP1 duplication, are less well understood. Methods: We developed and validated a mouse model of human CYFIP1 overexpression (CYFIP1 OE) using qPCR and western blot analysis. We performed a large battery of behavior testing on these mice, including ultrasonic vocalizations, three-chamber social assay, home-cage behavior, Y-maze, elevated plus maze, open field test, Morris water maze, fear conditioning, prepulse inhibition, and the hot plate assay. We also performed RNA sequencing and analysis on the basolateral amygdala. Results: Extensive behavioral testing in CYFIP1 OE mice reveals no changes in the core behaviors related to ASD: social interactions and repetitive behaviors. However, we did observe mild learning deficits and an exaggerated fear response. Using RNA sequencing of the basolateral amygdala, a region associated with fear response, we observed changes in pathways related to cytoskeletal regulation, oligodendrocytes, and myelination. We also identified GABA-A subunit composition changes in basolateral amygdala neurons, which are essential components of the neural fear conditioning circuit. Conclusion: Overall, this research identifies the behavioral and molecular consequences of CYFIP1 overexpression and how they contribute to the variable phenotype seen in Dup15q syndrome and in ASD patients with excess CYFIP1. En ligne : http://dx.doi.org/10.1186/s13229-019-0278-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402

Behavior in Prader-Willi syndrome: relationship to genetic subtypes and age / Elisabeth M. DYKENS in Journal of Child Psychology and Psychiatry, 49-9 (September 2008)  

Public ISBD [article]  inJournal of Child Psychology and Psychiatry > 49-9 (September 2008) . - p.1001-1008 Titre : Behavior in Prader-Willi syndrome: relationship to genetic subtypes and age Type de document : texte imprimé Auteurs : Elisabeth M. DYKENS, Auteur ; Elizabeth ROOF, Auteur Année de publication : 2008 Article en page(s) : p.1001-1008 Langues : Anglais (eng) Mots-clés : Prader-Willi-syndrome genetic-subtypes age CYFIP1 Index. décimale : PER Périodiques Résumé : Background: Some behavioral features of Prader-Willi syndrome (PWS) are associated with the major genetic subtypes of this disorder. While most agree that those with maternal uniparental disomy (UPD) have a distinctive cognitive and psychiatric profile, findings are more controversial regarding possible differences among persons who vary in paternal deletion size. Methods: Caregivers of 88 persons with PWS aged 5 to 51 years (M = 22 years) were administered measures of problem behavior, compulsivity, hyperphagia, and adaptive skills. The sample was well characterized as having relatively large, Type I (n = 26) or smaller, Type II (n = 29) deletions, or UPD (n = 33). Results: No significant behavioral differences were found between the Type I versus Type II deletion groups. Within each genetic subtype, however, differences emerged in how advancing age related to behavior. Although age did not emerge as a significant correlate of behavior in the Type II or UPD groups, in the Type I group age was consistently associated with lower problem behaviors, adaptive skills, and externalizing symptoms. Conclusion: Although differences between deletion subtypes were not found, significant within-subtype differences emerged in relationships between age and behavior. Negative associations between age and behavior in the Type I group only may relate to non-imprinted genes that are deleted in Type I but not Type II cases, including CYFIP1. Altered expression of CYFIP1 is seen in other developmental disabilities, including 15q disorders, and haploinsufficiency of CYFIP1 in Type I PWS cases may be associated with age-related phenotypic effects. Findings underscore the importance of a life-span perspective in phenotypic research. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2008.01913.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=559 [article] Behavior in Prader-Willi syndrome: relationship to genetic subtypes and age [texte imprimé] / Elisabeth M. DYKENS, Auteur ; Elizabeth ROOF, Auteur . - 2008 . - p.1001-1008. Langues : Anglais (eng) in Journal of Child Psychology and Psychiatry > 49-9 (September 2008) . - p.1001-1008 Mots-clés : Prader-Willi-syndrome genetic-subtypes age CYFIP1 Index. décimale : PER Périodiques Résumé : Background: Some behavioral features of Prader-Willi syndrome (PWS) are associated with the major genetic subtypes of this disorder. While most agree that those with maternal uniparental disomy (UPD) have a distinctive cognitive and psychiatric profile, findings are more controversial regarding possible differences among persons who vary in paternal deletion size. Methods: Caregivers of 88 persons with PWS aged 5 to 51 years (M = 22 years) were administered measures of problem behavior, compulsivity, hyperphagia, and adaptive skills. The sample was well characterized as having relatively large, Type I (n = 26) or smaller, Type II (n = 29) deletions, or UPD (n = 33). Results: No significant behavioral differences were found between the Type I versus Type II deletion groups. Within each genetic subtype, however, differences emerged in how advancing age related to behavior. Although age did not emerge as a significant correlate of behavior in the Type II or UPD groups, in the Type I group age was consistently associated with lower problem behaviors, adaptive skills, and externalizing symptoms. Conclusion: Although differences between deletion subtypes were not found, significant within-subtype differences emerged in relationships between age and behavior. Negative associations between age and behavior in the Type I group only may relate to non-imprinted genes that are deleted in Type I but not Type II cases, including CYFIP1. Altered expression of CYFIP1 is seen in other developmental disabilities, including 15q disorders, and haploinsufficiency of CYFIP1 in Type I PWS cases may be associated with age-related phenotypic effects. Findings underscore the importance of a life-span perspective in phenotypic research. En ligne : http://dx.doi.org/10.1111/j.1469-7610.2008.01913.x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=559