5 recherche sur le mot-clé 'Cntnap2'

CNTNAP2 Mutations in Autism / Olga PENAGARIKANO  

Public ISBD in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA Titre : CNTNAP2 Mutations in Autism Type de document : texte imprimé Auteurs : Olga PENAGARIKANO, Auteur Année de publication : 2016 Importance : p.177-188 Langues : Anglais (eng) Mots-clés : ASD  Autism  CDFE  CNTNAP2  Social behavior Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Autism spectrum disorders (ASDs) comprise a phenotypically and genetically heterogeneous condition characterized by deficits in social behavior and communication together with the presence of repetitive and restrictive behaviors. Autism spectrum disorder has a strong genetic component and mutations/variants in many genes have been identified as predisposing to ASD. The contactin-associated protein-like 2 (CNTNAP2) gene is one of the most replicated through interdisciplinary studies, supported by neurobiological, genetic, and imaging data. An understanding of the mechanistic link between genes and behavior is critical to developing targeted treatments. This chapter discusses the clinical genetics and current understanding of the biology of CNTNAP2 as related to ASD. Current multidisciplinary research approaches in both human subjects and animal models help us understand the pathophysiology associated with the goal of developing new treatments. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00012-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA CNTNAP2 Mutations in Autism [texte imprimé] / Olga PENAGARIKANO, Auteur . - 2016 . - p.177-188. Langues : Anglais (eng) Mots-clés : ASD  Autism  CDFE  CNTNAP2  Social behavior Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Autism spectrum disorders (ASDs) comprise a phenotypically and genetically heterogeneous condition characterized by deficits in social behavior and communication together with the presence of repetitive and restrictive behaviors. Autism spectrum disorder has a strong genetic component and mutations/variants in many genes have been identified as predisposing to ASD. The contactin-associated protein-like 2 (CNTNAP2) gene is one of the most replicated through interdisciplinary studies, supported by neurobiological, genetic, and imaging data. An understanding of the mechanistic link between genes and behavior is critical to developing targeted treatments. This chapter discusses the clinical genetics and current understanding of the biology of CNTNAP2 as related to ASD. Current multidisciplinary research approaches in both human subjects and animal models help us understand the pathophysiology associated with the goal of developing new treatments. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00012-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

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Association between CNTNAP2 polymorphisms and autism: A family-based study in the chinese han population and a meta-analysis combined with GWAS data of psychiatric genomics consortium / Tian ZHANG in Autism Research, 12-4 (April 2019)  

Public ISBD [article]  inAutism Research > 12-4 (April 2019) . - p.553-561 Titre : Association between CNTNAP2 polymorphisms and autism: A family-based study in the chinese han population and a meta-analysis combined with GWAS data of psychiatric genomics consortium Type de document : texte imprimé Auteurs : Tian ZHANG, Auteur ; Jishui ZHANG, Auteur ; Ziqi WANG, Auteur ; Meixiang JIA, Auteur ; Tianlan LU, Auteur ; Han WANG, Auteur ; Weihua YUE, Auteur ; Dai ZHANG, Auteur ; Jun LI, Auteur ; Lifang WANG, Auteur Article en page(s) : p.553-561 Langues : Anglais (eng) Mots-clés : Cntnap2  Pgc  autism  meta-analysis  polymorphism Index. décimale : PER Périodiques Résumé : Autism is a childhood neuropsychiatric disorder with evidence of a strong genetic component in the complex etiologies. Contactin-associated protein-like 2 (CNTNAP2), a member of the neurexin superfamily, plays an essential role in neural development. CNTNAP2 was considered as one of the most susceptible genes for autism spectrum disorder (ASD). Some studies indicated the association of CNTNAP2 with ASD, while others reported no association. Given the inconsistent results of the previous studies, we performed a family-based association study between 9 single-nucleotide polymorphisms (SNPs) of CNTNAP2 and autism in 640 autistic trios in the Chinese Han population. Then, an updated meta-analysis, combined with the data from Psychiatric Genomics Consortium (iPSYCH-PGC ASD, 2017) and available association studies, was conducted. No SNPs were significantly associated with autism in the Chinese Han population. In the meta-analysis, the two frequently reported SNPs (rs2710102 and rs7794745) showed no significant association with ASD. Therefore, CNTNAP2 polymorphisms might not be associated with autism. Autism Research 2019, 12: 553-561. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In present family-based association study, no single-nucleotide polymorphisms (SNPs) were significantly associated with autism in the Chinese Han population. In the updated meta-analysis, the association between the two frequently reported SNPs (rs2710102 and rs7794745) in CNTNAP2 and the risk of ASD was explored. However, the results showed no significant association. Therefore, our study suggested that CNTNAP2 polymorphisms might not be associated with autism. En ligne : https://dx.doi.org/10.1002/aur.2078 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=388 [article] Association between CNTNAP2 polymorphisms and autism: A family-based study in the chinese han population and a meta-analysis combined with GWAS data of psychiatric genomics consortium [texte imprimé] / Tian ZHANG, Auteur ; Jishui ZHANG, Auteur ; Ziqi WANG, Auteur ; Meixiang JIA, Auteur ; Tianlan LU, Auteur ; Han WANG, Auteur ; Weihua YUE, Auteur ; Dai ZHANG, Auteur ; Jun LI, Auteur ; Lifang WANG, Auteur . - p.553-561. Langues : Anglais (eng) in Autism Research > 12-4 (April 2019) . - p.553-561 Mots-clés : Cntnap2  Pgc  autism  meta-analysis  polymorphism Index. décimale : PER Périodiques Résumé : Autism is a childhood neuropsychiatric disorder with evidence of a strong genetic component in the complex etiologies. Contactin-associated protein-like 2 (CNTNAP2), a member of the neurexin superfamily, plays an essential role in neural development. CNTNAP2 was considered as one of the most susceptible genes for autism spectrum disorder (ASD). Some studies indicated the association of CNTNAP2 with ASD, while others reported no association. Given the inconsistent results of the previous studies, we performed a family-based association study between 9 single-nucleotide polymorphisms (SNPs) of CNTNAP2 and autism in 640 autistic trios in the Chinese Han population. Then, an updated meta-analysis, combined with the data from Psychiatric Genomics Consortium (iPSYCH-PGC ASD, 2017) and available association studies, was conducted. No SNPs were significantly associated with autism in the Chinese Han population. In the meta-analysis, the two frequently reported SNPs (rs2710102 and rs7794745) showed no significant association with ASD. Therefore, CNTNAP2 polymorphisms might not be associated with autism. Autism Research 2019, 12: 553-561. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In present family-based association study, no single-nucleotide polymorphisms (SNPs) were significantly associated with autism in the Chinese Han population. In the updated meta-analysis, the association between the two frequently reported SNPs (rs2710102 and rs7794745) in CNTNAP2 and the risk of ASD was explored. However, the results showed no significant association. Therefore, our study suggested that CNTNAP2 polymorphisms might not be associated with autism. En ligne : https://dx.doi.org/10.1002/aur.2078 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=388

Loss of Cntnap2 in the Rat Causes Autism-Related Alterations in Social Interactions, Stereotypic Behavior, and Sensory Processing / Kaela E. SCOTT in Autism Research, 13-10 (October 2020)  

Public ISBD [article]  inAutism Research > 13-10 (October 2020) . - p.1698-1717 Titre : Loss of Cntnap2 in the Rat Causes Autism-Related Alterations in Social Interactions, Stereotypic Behavior, and Sensory Processing Type de document : texte imprimé Auteurs : Kaela E. SCOTT, Auteur ; Karnig KAZAZIAN, Auteur ; Rajkamalpreet S. MANN, Auteur ; Dorit MÖHRLE, Auteur ; Ashley L. SCHORMANS, Auteur ; Susanne SCHMID, Auteur ; Brian L. ALLMAN, Auteur Article en page(s) : p.1698-1717 Langues : Anglais (eng) Mots-clés : Cntnap2  animal model  autism spectrum disorder  behavior  sensory  social  startle Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is characterized by social interaction and communication impairments, as well as restrictive/repetitive patterns of behavior, interests or activities, which can coexist with intellectual disability and altered sensory processing. To study the mechanisms underlying these core features of ASD, preclinical research has developed animal models with manipulations in ASD-linked genes, such as CNTNAP2. In order to fully interpret the findings from mechanistic studies, the extent to which these models display behaviors consistent with ASD must be determined. Toward that goal, we conducted an investigation of the consequences of a functional loss of Cntnap2 on ASD-related behaviors by comparing the performance of rats with a homozygous or heterozygous knockout of Cntnap2 to their wildtype littermates across a comprehensive test battery. Cntnap2(-/-) rats showed deficits in sociability and social novelty, and they displayed repetitive circling and hyperlocomotion. Moreover, Cntnap2(-/-) rats demonstrated exaggerated acoustic startle responses, increased avoidance to sounds of moderate intensity, and a lack of rapid audiovisual temporal recalibration; indicating changes in sensory processing at both the pre-attentive and perceptual levels. Notably, sensory behaviors requiring learned associations did not reveal genotypic differences, whereas tasks relying on automatic/implicit behaviors did. Ultimately, because these collective alterations in social, stereotypic, and sensory behaviors are phenotypically similar to those reported in individuals with ASD, our results establish the Cntnap2 knockout rat model as an effective platform to study not only the molecular and cellular mechanisms associated with ASD, but also the complex relationship between altered sensory processing and other core ASD-related behaviors. LAY SUMMARY: Autism spectrum disorder (ASD) is characterized by social interaction differences, and restrictive/repetitive patterns of behavior. We studied the behavioral alterations caused by the loss of an autism-linked gene, Cntnap2, in the rat to determine how mutations in this gene contribute to autism-related behaviors. We show the loss of Cntnap2 leads to changes in social, stereotypic, and sensory behaviors, indicating this rat model can be used to better understand the brain changes underlying ASD. Autism Res 2020, 13: 1698-1717. © 2020 International Society for Autism Research and Wiley Periodicals LLC. En ligne : http://dx.doi.org/10.1002/aur.2364 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431 [article] Loss of Cntnap2 in the Rat Causes Autism-Related Alterations in Social Interactions, Stereotypic Behavior, and Sensory Processing [texte imprimé] / Kaela E. SCOTT, Auteur ; Karnig KAZAZIAN, Auteur ; Rajkamalpreet S. MANN, Auteur ; Dorit MÖHRLE, Auteur ; Ashley L. SCHORMANS, Auteur ; Susanne SCHMID, Auteur ; Brian L. ALLMAN, Auteur . - p.1698-1717. Langues : Anglais (eng) in Autism Research > 13-10 (October 2020) . - p.1698-1717 Mots-clés : Cntnap2  animal model  autism spectrum disorder  behavior  sensory  social  startle Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is characterized by social interaction and communication impairments, as well as restrictive/repetitive patterns of behavior, interests or activities, which can coexist with intellectual disability and altered sensory processing. To study the mechanisms underlying these core features of ASD, preclinical research has developed animal models with manipulations in ASD-linked genes, such as CNTNAP2. In order to fully interpret the findings from mechanistic studies, the extent to which these models display behaviors consistent with ASD must be determined. Toward that goal, we conducted an investigation of the consequences of a functional loss of Cntnap2 on ASD-related behaviors by comparing the performance of rats with a homozygous or heterozygous knockout of Cntnap2 to their wildtype littermates across a comprehensive test battery. Cntnap2(-/-) rats showed deficits in sociability and social novelty, and they displayed repetitive circling and hyperlocomotion. Moreover, Cntnap2(-/-) rats demonstrated exaggerated acoustic startle responses, increased avoidance to sounds of moderate intensity, and a lack of rapid audiovisual temporal recalibration; indicating changes in sensory processing at both the pre-attentive and perceptual levels. Notably, sensory behaviors requiring learned associations did not reveal genotypic differences, whereas tasks relying on automatic/implicit behaviors did. Ultimately, because these collective alterations in social, stereotypic, and sensory behaviors are phenotypically similar to those reported in individuals with ASD, our results establish the Cntnap2 knockout rat model as an effective platform to study not only the molecular and cellular mechanisms associated with ASD, but also the complex relationship between altered sensory processing and other core ASD-related behaviors. LAY SUMMARY: Autism spectrum disorder (ASD) is characterized by social interaction differences, and restrictive/repetitive patterns of behavior. We studied the behavioral alterations caused by the loss of an autism-linked gene, Cntnap2, in the rat to determine how mutations in this gene contribute to autism-related behaviors. We show the loss of Cntnap2 leads to changes in social, stereotypic, and sensory behaviors, indicating this rat model can be used to better understand the brain changes underlying ASD. Autism Res 2020, 13: 1698-1717. © 2020 International Society for Autism Research and Wiley Periodicals LLC. En ligne : http://dx.doi.org/10.1002/aur.2364 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=431

The role of the CNTNAP2 gene in the development of autism spectrum disorder / Ilnur S. SABIROV ; Liliya R. SAFIULLINA ; Dmitriy O. NIKITIN ; Irina I. SEMINA ; Tim REES ; Denis O. FESENKO ; Ildus I. AHMETOV in Research in Autism Spectrum Disorders, 114 (June 2024)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 114 (June 2024) . - p.102409 Titre : The role of the CNTNAP2 gene in the development of autism spectrum disorder Type de document : texte imprimé Auteurs : Ilnur S. SABIROV, Auteur ; Liliya R. SAFIULLINA, Auteur ; Dmitriy O. NIKITIN, Auteur ; Irina I. SEMINA, Auteur ; Tim REES, Auteur ; Denis O. FESENKO, Auteur ; Ildus I. AHMETOV, Auteur Année de publication : 2024 Article en page(s) : p.102409 Langues : Anglais (eng) Mots-clés : Autism  ASD  Cntnap2  Polymorphism  Gene expression  Valproic acid Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which genetic and environmental factors interact in its development. Research suggests that the contactin associated protein 2 (CNTNAP2) gene may play a role in ASD pathophysiology, yet more studies involving human participants and animal models of autism are needed. One such model may be the use of prenatal valproic acid (VPA) model to induce autism-like behaviors in offspring rats. The aim of this study was twofold: (1) to examine the association of the CNTNAP2 gene rs2710102 variant with ASD in children; and (2) to examine the effect of prenatal exposure to VPA on Cntnap2 gene expression in the rat brain. The study included 167 children of European ancestry-81 diagnosed with ASD (20 girls, 61 boys; age 4.9 + 1.4 years) and 86 controls (44 girls, 42 boys; 5.1 + 1.2 years). In vivo experiments were conducted in 80 rats (40 with the VPA model of autism), with Cntnap2 gene expression analysis in the amygdala, hippocampus, prefrontal cortex, and cerebellum. Results demonstrated that the frequency of the CNTNAP2 gene rs2710102 GG genotype was significantly higher in children with ASD when compared with controls (33.3 vs 19.8%; OR=2.03, 95%CI [1.004, 4.102], p = 0.035), although, potentially due to bias in cohort selection, in the ASD children this polymorphism did not meet Hardy-Weinberg expectations ( 2 =5.40, p = 0.02). In addition, Cntnap2 gene expression was significantly lower (p < 0.01) in the amygdala and hippocampus of VPA rats when compared with controls, regardless of sex. These results support previous research and provide evidence for the CNTNAP2 gene as a risk factor for ASD. En ligne : https://doi.org/10.1016/j.rasd.2024.102409 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=529 [article] The role of the CNTNAP2 gene in the development of autism spectrum disorder [texte imprimé] / Ilnur S. SABIROV, Auteur ; Liliya R. SAFIULLINA, Auteur ; Dmitriy O. NIKITIN, Auteur ; Irina I. SEMINA, Auteur ; Tim REES, Auteur ; Denis O. FESENKO, Auteur ; Ildus I. AHMETOV, Auteur . - 2024 . - p.102409. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 114 (June 2024) . - p.102409 Mots-clés : Autism  ASD  Cntnap2  Polymorphism  Gene expression  Valproic acid Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a neurodevelopmental disorder in which genetic and environmental factors interact in its development. Research suggests that the contactin associated protein 2 (CNTNAP2) gene may play a role in ASD pathophysiology, yet more studies involving human participants and animal models of autism are needed. One such model may be the use of prenatal valproic acid (VPA) model to induce autism-like behaviors in offspring rats. The aim of this study was twofold: (1) to examine the association of the CNTNAP2 gene rs2710102 variant with ASD in children; and (2) to examine the effect of prenatal exposure to VPA on Cntnap2 gene expression in the rat brain. The study included 167 children of European ancestry-81 diagnosed with ASD (20 girls, 61 boys; age 4.9 + 1.4 years) and 86 controls (44 girls, 42 boys; 5.1 + 1.2 years). In vivo experiments were conducted in 80 rats (40 with the VPA model of autism), with Cntnap2 gene expression analysis in the amygdala, hippocampus, prefrontal cortex, and cerebellum. Results demonstrated that the frequency of the CNTNAP2 gene rs2710102 GG genotype was significantly higher in children with ASD when compared with controls (33.3 vs 19.8%; OR=2.03, 95%CI [1.004, 4.102], p = 0.035), although, potentially due to bias in cohort selection, in the ASD children this polymorphism did not meet Hardy-Weinberg expectations ( 2 =5.40, p = 0.02). In addition, Cntnap2 gene expression was significantly lower (p < 0.01) in the amygdala and hippocampus of VPA rats when compared with controls, regardless of sex. These results support previous research and provide evidence for the CNTNAP2 gene as a risk factor for ASD. En ligne : https://doi.org/10.1016/j.rasd.2024.102409 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=529

Age-Dependent Effects of Loss of Contactin-Associated Protein-Like 2, an Autism-Associated Gene, on the Acquisition and Recall of Fear Memory / A. BERNS ; Myles JONES ; A. TOWNSEND ; A.K. EAGEN ; Sarah L. FERRI ; D.R. LANGBEHN ; H. JANOUSCHEK in Autism Research, 18-5 (May 2025)  

Public ISBD [article]  inAutism Research > 18-5 (May 2025) . - p.1011-1023 Titre : Age-Dependent Effects of Loss of Contactin-Associated Protein-Like 2, an Autism-Associated Gene, on the Acquisition and Recall of Fear Memory Type de document : texte imprimé Auteurs : A. BERNS, Auteur ; Myles JONES, Auteur ; A. TOWNSEND, Auteur ; A.K. EAGEN, Auteur ; Sarah L. FERRI, Auteur ; D.R. LANGBEHN, Auteur ; H. JANOUSCHEK, Auteur Article en page(s) : p.1011-1023 Langues : Anglais (eng) Mots-clés : anxiety  autism spectrum disorder  CASPR2  Cntnap2  development  fear  fear conditioning  memory Index. décimale : PER Périodiques Résumé : ABSTRACT The contactin-associated protein-like 2 (Cntnap2) gene is relevant to autism spectrum disorder (ASD), which is associated with age-specific structural alterations in limbic brain regions. The Cntnap2 gene encodes for the contactin-associated protein-like 2 (CASPR2) protein, and CASPR2 protein levels are high in the amygdala, a limbic region that is essential for the processing of fear and anxiety. In humans, reduced levels of this protein arising from CNTNAP2 mutations could potentially account for the autism-associated increase in fear and anxiety. Here, we report the extent to which loss of CASPR2 in mice contributes to the development of fear- and anxiety-related behaviors. Pavlovian fear conditioning experiments revealed that loss of CASPR2 has age-dependent effects on the acquisition of fear memory, recall of both cue-evoked and context-related fear memory, and stability of cue-evoked fear memory. Additionally, data from the elevated zero maze suggest that CASPR2 deficiency contributes to anxiety-related behaviors, especially in juvenile (29-day old) mice. These are the first reports of age-dependent effects of CASPR2 deficiency on fear and anxiety-related behaviors, and they set the stage for a better understanding of developmental alterations of fear and anxiety in ASD. En ligne : https://doi.org/10.1002/aur.70034 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=558 [article] Age-Dependent Effects of Loss of Contactin-Associated Protein-Like 2, an Autism-Associated Gene, on the Acquisition and Recall of Fear Memory [texte imprimé] / A. BERNS, Auteur ; Myles JONES, Auteur ; A. TOWNSEND, Auteur ; A.K. EAGEN, Auteur ; Sarah L. FERRI, Auteur ; D.R. LANGBEHN, Auteur ; H. JANOUSCHEK, Auteur . - p.1011-1023. Langues : Anglais (eng) in Autism Research > 18-5 (May 2025) . - p.1011-1023 Mots-clés : anxiety  autism spectrum disorder  CASPR2  Cntnap2  development  fear  fear conditioning  memory Index. décimale : PER Périodiques Résumé : ABSTRACT The contactin-associated protein-like 2 (Cntnap2) gene is relevant to autism spectrum disorder (ASD), which is associated with age-specific structural alterations in limbic brain regions. The Cntnap2 gene encodes for the contactin-associated protein-like 2 (CASPR2) protein, and CASPR2 protein levels are high in the amygdala, a limbic region that is essential for the processing of fear and anxiety. In humans, reduced levels of this protein arising from CNTNAP2 mutations could potentially account for the autism-associated increase in fear and anxiety. Here, we report the extent to which loss of CASPR2 in mice contributes to the development of fear- and anxiety-related behaviors. Pavlovian fear conditioning experiments revealed that loss of CASPR2 has age-dependent effects on the acquisition of fear memory, recall of both cue-evoked and context-related fear memory, and stability of cue-evoked fear memory. Additionally, data from the elevated zero maze suggest that CASPR2 deficiency contributes to anxiety-related behaviors, especially in juvenile (29-day old) mice. These are the first reports of age-dependent effects of CASPR2 deficiency on fear and anxiety-related behaviors, and they set the stage for a better understanding of developmental alterations of fear and anxiety in ASD. En ligne : https://doi.org/10.1002/aur.70034 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=558