6 recherche sur le mot-clé 'Ultrasonic vocalization'

16p11.2 Deletion Syndrome Mice Display Sensory and Ultrasonic Vocalization Deficits During Social Interactions / Mu YANG in Autism Research, 8-5 (October 2015)  

Public ISBD [article]  inAutism Research > 8-5 (October 2015) . - p.507-521 Titre : 16p11.2 Deletion Syndrome Mice Display Sensory and Ultrasonic Vocalization Deficits During Social Interactions Type de document : texte imprimé Auteurs : Mu YANG, Auteur ; Elena J. MAHRT, Auteur ; Freeman LEWIS, Auteur ; Gillian FOLEY, Auteur ; Thomas PORTMANN, Auteur ; Ricardo E. DOLMETSCH, Auteur ; Christine V. PORTFORS, Auteur ; Jacqueline N. CRAWLEY, Auteur Article en page(s) : p.507-521 Langues : Anglais (eng) Mots-clés : mouse model of autism  16p11.2 deletion  ultrasonic vocalization  social Interaction  autism Index. décimale : PER Périodiques Résumé : Recurrent deletions and duplications at chromosomal region 16p11.2 are variably associated with speech delay, autism spectrum disorder, developmental delay, schizophrenia, and cognitive impairments. Social communication deficits are a primary diagnostic symptom of autism. Here we investigated ultrasonic vocalizations (USVs) in young adult male 16p11.2 deletion mice during a novel three-phase male–female social interaction test that detects vocalizations emitted by a male in the presence of an estrous female, how the male changes its calling when the female is suddenly absent, and the extent to which calls resume when the female returns. Strikingly fewer vocalizations were detected in two independent cohorts of 16p11.2 heterozygous deletion males (+/−) during the first exposure to an unfamiliar estrous female, as compared to wildtype littermates (+/+). When the female was removed, +/+ emitted calls, but at a much lower level, whereas +/− males called minimally. Sensory and motor abnormalities were detected in +/−, including higher nociceptive thresholds, a complete absence of acoustic startle responses, and hearing loss in all +/− as confirmed by lack of auditory brainstem responses to frequencies between 8 and 100 kHz. Stereotyped circling and backflipping appeared in a small percentage of individuals, as previously reported. However, these sensory and motor phenotypes could not directly explain the low vocalizations in 16p11.2 deletion mice, since (a) +/− males displayed normal abilities to emit vocalizations when the female was subsequently reintroduced, and (b) +/− vocalized less than +/+ to social odor cues delivered on an inanimate cotton swab. Our findings support the concept that mouse USVs in social settings represent a response to social cues, and that 16p11.2 deletion mice are deficient in their initial USVs responses to novel social cues. Autism Res 2015, 8: 507–521. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1465 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=270 [article] 16p11.2 Deletion Syndrome Mice Display Sensory and Ultrasonic Vocalization Deficits During Social Interactions [texte imprimé] / Mu YANG, Auteur ; Elena J. MAHRT, Auteur ; Freeman LEWIS, Auteur ; Gillian FOLEY, Auteur ; Thomas PORTMANN, Auteur ; Ricardo E. DOLMETSCH, Auteur ; Christine V. PORTFORS, Auteur ; Jacqueline N. CRAWLEY, Auteur . - p.507-521. Langues : Anglais (eng) in Autism Research > 8-5 (October 2015) . - p.507-521 Mots-clés : mouse model of autism  16p11.2 deletion  ultrasonic vocalization  social Interaction  autism Index. décimale : PER Périodiques Résumé : Recurrent deletions and duplications at chromosomal region 16p11.2 are variably associated with speech delay, autism spectrum disorder, developmental delay, schizophrenia, and cognitive impairments. Social communication deficits are a primary diagnostic symptom of autism. Here we investigated ultrasonic vocalizations (USVs) in young adult male 16p11.2 deletion mice during a novel three-phase male–female social interaction test that detects vocalizations emitted by a male in the presence of an estrous female, how the male changes its calling when the female is suddenly absent, and the extent to which calls resume when the female returns. Strikingly fewer vocalizations were detected in two independent cohorts of 16p11.2 heterozygous deletion males (+/−) during the first exposure to an unfamiliar estrous female, as compared to wildtype littermates (+/+). When the female was removed, +/+ emitted calls, but at a much lower level, whereas +/− males called minimally. Sensory and motor abnormalities were detected in +/−, including higher nociceptive thresholds, a complete absence of acoustic startle responses, and hearing loss in all +/− as confirmed by lack of auditory brainstem responses to frequencies between 8 and 100 kHz. Stereotyped circling and backflipping appeared in a small percentage of individuals, as previously reported. However, these sensory and motor phenotypes could not directly explain the low vocalizations in 16p11.2 deletion mice, since (a) +/− males displayed normal abilities to emit vocalizations when the female was subsequently reintroduced, and (b) +/− vocalized less than +/+ to social odor cues delivered on an inanimate cotton swab. Our findings support the concept that mouse USVs in social settings represent a response to social cues, and that 16p11.2 deletion mice are deficient in their initial USVs responses to novel social cues. Autism Res 2015, 8: 507–521. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1465 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=270

MEK inhibition ameliorates social behavior phenotypes in a Spred1 knockout mouse model for RASopathy disorders / Sarah C. BORRIE in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 53 p. Titre : MEK inhibition ameliorates social behavior phenotypes in a Spred1 knockout mouse model for RASopathy disorders Type de document : texte imprimé Auteurs : Sarah C. BORRIE, Auteur ; Ellen PLASSCHAERT, Auteur ; Zsuzsanna CALLAERTS-VEGH, Auteur ; Akihiko YOSHIMURA, Auteur ; Rudi D'HOOGE, Auteur ; Ype ELGERSMA, Auteur ; Steven A. KUSHNER, Auteur ; Eric LEGIUS, Auteur ; Hilde BREMS, Auteur Article en page(s) : 53 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Neurofibromatosis type 1  RASopathy  Social dominance  Spred1  Ultrasonic vocalization  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: RASopathies are a group of disorders that result from mutations in genes coding for proteins involved in regulating the Ras-MAPK signaling pathway, and have an increased incidence of autism spectrum disorder (ASD). Legius syndrome is a rare RASopathy caused by loss-of-function mutations in the SPRED1 gene. The patient phenotype is similar to, but milder than, Neurofibromatosis type 1-another RASopathy caused by loss-of-function mutations in the NF1 gene. RASopathies exhibit increased activation of Ras-MAPK signaling and commonly manifest with cognitive impairments and ASD. Here, we investigated if a Spred1-/- mouse model for Legius syndrome recapitulates ASD-like symptoms, and whether targeting the Ras-MAPK pathway has therapeutic potential in this RASopathy mouse model. METHODS: We investigated social and communicative behaviors in Spred1-/- mice and probed therapeutic mechanisms underlying the observed behavioral phenotypes by pharmacological targeting of the Ras-MAPK pathway with the MEK inhibitor PD325901. RESULTS: Spred1-/- mice have robust increases in social dominance in the automated tube test and reduced adult ultrasonic vocalizations during social communication. Neonatal ultrasonic vocalization was also altered, with significant differences in spectral properties. Spred1-/- mice also exhibit impaired nesting behavior. Acute MEK inhibitor treatment in adulthood with PD325901 reversed the enhanced social dominance in Spred1-/- mice to normal levels, and improved nesting behavior in adult Spred1-/- mice. LIMITATIONS: This study used an acute treatment protocol to administer the drug. It is not known what the effects of longer-term treatment would be on behavior. Further studies titrating the lowest dose of this drug that is required to alter Spred1-/- social behavior are still required. Finally, our findings are in a homozygous mouse model, whereas patients carry heterozygous mutations. These factors should be considered before any translational conclusions are drawn. CONCLUSIONS: These results demonstrate for the first time that social behavior phenotypes in a mouse model for RASopathies (Spred1-/-) can be acutely reversed. This highlights a key role for Ras-MAPK dysregulation in mediating social behavior phenotypes in mouse models for ASD, suggesting that proper regulation of Ras-MAPK signaling is important for social behavior. En ligne : http://dx.doi.org/10.1186/s13229-021-00458-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] MEK inhibition ameliorates social behavior phenotypes in a Spred1 knockout mouse model for RASopathy disorders [texte imprimé] / Sarah C. BORRIE, Auteur ; Ellen PLASSCHAERT, Auteur ; Zsuzsanna CALLAERTS-VEGH, Auteur ; Akihiko YOSHIMURA, Auteur ; Rudi D'HOOGE, Auteur ; Ype ELGERSMA, Auteur ; Steven A. KUSHNER, Auteur ; Eric LEGIUS, Auteur ; Hilde BREMS, Auteur . - 53 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 53 p. Mots-clés : Autism spectrum disorder  Neurofibromatosis type 1  RASopathy  Social dominance  Spred1  Ultrasonic vocalization  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: RASopathies are a group of disorders that result from mutations in genes coding for proteins involved in regulating the Ras-MAPK signaling pathway, and have an increased incidence of autism spectrum disorder (ASD). Legius syndrome is a rare RASopathy caused by loss-of-function mutations in the SPRED1 gene. The patient phenotype is similar to, but milder than, Neurofibromatosis type 1-another RASopathy caused by loss-of-function mutations in the NF1 gene. RASopathies exhibit increased activation of Ras-MAPK signaling and commonly manifest with cognitive impairments and ASD. Here, we investigated if a Spred1-/- mouse model for Legius syndrome recapitulates ASD-like symptoms, and whether targeting the Ras-MAPK pathway has therapeutic potential in this RASopathy mouse model. METHODS: We investigated social and communicative behaviors in Spred1-/- mice and probed therapeutic mechanisms underlying the observed behavioral phenotypes by pharmacological targeting of the Ras-MAPK pathway with the MEK inhibitor PD325901. RESULTS: Spred1-/- mice have robust increases in social dominance in the automated tube test and reduced adult ultrasonic vocalizations during social communication. Neonatal ultrasonic vocalization was also altered, with significant differences in spectral properties. Spred1-/- mice also exhibit impaired nesting behavior. Acute MEK inhibitor treatment in adulthood with PD325901 reversed the enhanced social dominance in Spred1-/- mice to normal levels, and improved nesting behavior in adult Spred1-/- mice. LIMITATIONS: This study used an acute treatment protocol to administer the drug. It is not known what the effects of longer-term treatment would be on behavior. Further studies titrating the lowest dose of this drug that is required to alter Spred1-/- social behavior are still required. Finally, our findings are in a homozygous mouse model, whereas patients carry heterozygous mutations. These factors should be considered before any translational conclusions are drawn. CONCLUSIONS: These results demonstrate for the first time that social behavior phenotypes in a mouse model for RASopathies (Spred1-/-) can be acutely reversed. This highlights a key role for Ras-MAPK dysregulation in mediating social behavior phenotypes in mouse models for ASD, suggesting that proper regulation of Ras-MAPK signaling is important for social behavior. En ligne : http://dx.doi.org/10.1186/s13229-021-00458-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study / Axel KRUG in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 54 p. Titre : Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study Type de document : texte imprimé Auteurs : Axel KRUG, Auteur ; Markus WÖHR, Auteur ; Dominik SEFFER, Auteur ; Henrike RIPPBERGER, Auteur ; A. Özge SUNGUR, Auteur ; Bruno DIETSCHE, Auteur ; Frederike STEIN, Auteur ; Sugirthan SIVALINGAM, Auteur ; Andreas J. FORSTNER, Auteur ; Stephanie H. WITT, Auteur ; Helene DUKAL, Auteur ; Fabian STREIT, Auteur ; Anna MAASER, Auteur ; Stefanie HEILMANN-HEIMBACH, Auteur ; Till F.M. ANDLAUER, Auteur ; Stefan HERMS, Auteur ; Per HOFFMANN, Auteur ; Marcella RIETSCHEL, Auteur ; Markus M. NÖTHEN, Auteur ; Martin LACKINGER, Auteur ; Gerhard SCHRATT, Auteur ; Michael KOCH, Auteur ; Rainer K.W. SCHWARTING, Auteur ; Tilo KIRCHER, Auteur Article en page(s) : 54 p. Langues : Anglais (eng) Mots-clés : Advanced paternal age (APA)  Diffusion tension imaging (DTI)  Social behavior  Ultrasonic vocalization  Voxel-based morphometry (VBM) Index. décimale : PER Périodiques Résumé : Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N = 677). Paternal age was further positively associated with gray matter volume (VBM, N = 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI, N = 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction. En ligne : http://dx.doi.org/10.1186/s13229-020-00345-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 [article] Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study [texte imprimé] / Axel KRUG, Auteur ; Markus WÖHR, Auteur ; Dominik SEFFER, Auteur ; Henrike RIPPBERGER, Auteur ; A. Özge SUNGUR, Auteur ; Bruno DIETSCHE, Auteur ; Frederike STEIN, Auteur ; Sugirthan SIVALINGAM, Auteur ; Andreas J. FORSTNER, Auteur ; Stephanie H. WITT, Auteur ; Helene DUKAL, Auteur ; Fabian STREIT, Auteur ; Anna MAASER, Auteur ; Stefanie HEILMANN-HEIMBACH, Auteur ; Till F.M. ANDLAUER, Auteur ; Stefan HERMS, Auteur ; Per HOFFMANN, Auteur ; Marcella RIETSCHEL, Auteur ; Markus M. NÖTHEN, Auteur ; Martin LACKINGER, Auteur ; Gerhard SCHRATT, Auteur ; Michael KOCH, Auteur ; Rainer K.W. SCHWARTING, Auteur ; Tilo KIRCHER, Auteur . - 54 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 54 p. Mots-clés : Advanced paternal age (APA)  Diffusion tension imaging (DTI)  Social behavior  Ultrasonic vocalization  Voxel-based morphometry (VBM) Index. décimale : PER Périodiques Résumé : Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N = 677). Paternal age was further positively associated with gray matter volume (VBM, N = 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI, N = 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction. En ligne : http://dx.doi.org/10.1186/s13229-020-00345-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427

Characterization of early markers of disease in the mouse model of mucopolysaccharidosis IIIB / Katherine B. MCCULLOUGH in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Characterization of early markers of disease in the mouse model of mucopolysaccharidosis IIIB Type de document : texte imprimé Auteurs : Katherine B. MCCULLOUGH, Auteur ; Amanda TITUS, Auteur ; Kate REARDON, Auteur ; Sara CONYERS, Auteur ; Joseph D. DOUGHERTY, Auteur ; Xia GE, Auteur ; Joel R. GARBOW, Auteur ; Patricia DICKSON, Auteur ; Carla M. YUEDE, Auteur ; Susan E. MALONEY, Auteur Langues : Anglais (eng) Mots-clés : Humans  Animals  Adult  Child  Mucopolysaccharidosis III/genetics/pathology  Diffusion Tensor Imaging  Brain  Disease Models, Animal  Treatment Outcome  Aggression  Dominance  Fear conditioning  Gait  Lysosomal storage disorder  Mri/dti  Mucopolysaccharidosis IIIB  Sanfilippo B  Startle response  Ultrasonic vocalization Index. décimale : PER Périodiques Résumé : BACKGROUND: Mucopolysaccharidosis (MPS) IIIB, also known as Sanfilippo Syndrome B, is a devastating childhood disease. Unfortunately, there are currently no available treatments for MPS IIIB patients. Yet, animal models of lysosomal storage diseases have been valuable tools in identifying promising avenues of treatment. Enzyme replacement therapy, gene therapy, and bone marrow transplant have all shown efficacy in the MPS IIIB model systems. A ubiquitous finding across rodent models of lysosomal storage diseases is that the best treatment outcomes resulted from intervention prior to symptom onset. Therefore, the aim of the current study was to identify early markers of disease in the MPS IIIB mouse model as well as examine clinically-relevant behavioral domains not yet explored in this model. METHODS: Using the MPS IIIB mouse model, we explored early developmental trajectories of communication and gait, and later social behavior, fear-related startle and conditioning, and visual capabilities. In addition, we examined brain structure and function via magnetic resonance imaging and diffusion tensor imaging. RESULTS: We observed reduced maternal isolation-induced ultrasonic vocalizations in MPS IIIB mice relative to controls, as well as disruption in a number of the spectrotemporal features. MPS IIIB also exhibited disrupted thermoregulation during the first two postnatal weeks without any differences in body weight. The developmental trajectories of gait were largely normal. In early adulthood, we observed intact visual acuity and sociability yet a more submissive phenotype, increased aggressive behavior, and decreased social sniffing relative to controls. MPS IIIB mice showed greater inhibition of startle in response to a pretone with a decrease in overall startle response and reduced cued fear memory. MPS IIIB also weighed significantly more than controls throughout adulthood and showed larger whole brain volumes and normalized regional volumes with intact tissue integrity as measured with magnetic resonance and diffusion tensor imaging, respectively. CONCLUSIONS: Together, these results indicate disease markers are present as early as the first two weeks postnatal in this model. Further, this model recapitulates social, sensory and fear-related clinical features. Our study using a mouse model of MPS IIIB provides essential baseline information that will be useful in future evaluations of potential treatments. En ligne : https://dx.doi.org/10.1186/s11689-024-09534-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Characterization of early markers of disease in the mouse model of mucopolysaccharidosis IIIB [texte imprimé] / Katherine B. MCCULLOUGH, Auteur ; Amanda TITUS, Auteur ; Kate REARDON, Auteur ; Sara CONYERS, Auteur ; Joseph D. DOUGHERTY, Auteur ; Xia GE, Auteur ; Joel R. GARBOW, Auteur ; Patricia DICKSON, Auteur ; Carla M. YUEDE, Auteur ; Susan E. MALONEY, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Humans  Animals  Adult  Child  Mucopolysaccharidosis III/genetics/pathology  Diffusion Tensor Imaging  Brain  Disease Models, Animal  Treatment Outcome  Aggression  Dominance  Fear conditioning  Gait  Lysosomal storage disorder  Mri/dti  Mucopolysaccharidosis IIIB  Sanfilippo B  Startle response  Ultrasonic vocalization Index. décimale : PER Périodiques Résumé : BACKGROUND: Mucopolysaccharidosis (MPS) IIIB, also known as Sanfilippo Syndrome B, is a devastating childhood disease. Unfortunately, there are currently no available treatments for MPS IIIB patients. Yet, animal models of lysosomal storage diseases have been valuable tools in identifying promising avenues of treatment. Enzyme replacement therapy, gene therapy, and bone marrow transplant have all shown efficacy in the MPS IIIB model systems. A ubiquitous finding across rodent models of lysosomal storage diseases is that the best treatment outcomes resulted from intervention prior to symptom onset. Therefore, the aim of the current study was to identify early markers of disease in the MPS IIIB mouse model as well as examine clinically-relevant behavioral domains not yet explored in this model. METHODS: Using the MPS IIIB mouse model, we explored early developmental trajectories of communication and gait, and later social behavior, fear-related startle and conditioning, and visual capabilities. In addition, we examined brain structure and function via magnetic resonance imaging and diffusion tensor imaging. RESULTS: We observed reduced maternal isolation-induced ultrasonic vocalizations in MPS IIIB mice relative to controls, as well as disruption in a number of the spectrotemporal features. MPS IIIB also exhibited disrupted thermoregulation during the first two postnatal weeks without any differences in body weight. The developmental trajectories of gait were largely normal. In early adulthood, we observed intact visual acuity and sociability yet a more submissive phenotype, increased aggressive behavior, and decreased social sniffing relative to controls. MPS IIIB mice showed greater inhibition of startle in response to a pretone with a decrease in overall startle response and reduced cued fear memory. MPS IIIB also weighed significantly more than controls throughout adulthood and showed larger whole brain volumes and normalized regional volumes with intact tissue integrity as measured with magnetic resonance and diffusion tensor imaging, respectively. CONCLUSIONS: Together, these results indicate disease markers are present as early as the first two weeks postnatal in this model. Further, this model recapitulates social, sensory and fear-related clinical features. Our study using a mouse model of MPS IIIB provides essential baseline information that will be useful in future evaluations of potential treatments. En ligne : https://dx.doi.org/10.1186/s11689-024-09534-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context / A. Özge SUNGUR in Autism Research, 9-6 (June 2016)  

Public ISBD [article]  inAutism Research > 9-6 (June 2016) . - p.696-709 Titre : Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context Type de document : texte imprimé Auteurs : A. Özge SUNGUR, Auteur ; Rainer K.W. SCHWARTING, Auteur ; Markus WÖHR, Auteur Article en page(s) : p.696-709 Langues : Anglais (eng) Mots-clés : animal model  postsynaptic density  neurodevelopmental disorders  autism  communication  ultrasonic vocalization  social context Index. décimale : PER Périodiques Résumé : Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation-induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1−/− null mutant, Shank1+/− heterozygous, and Shank1+/+ wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD-related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1−/− pups vocalized less and displayed a delay in the typical inverted U-shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype-dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696–709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1564 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=290 [article] Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context [texte imprimé] / A. Özge SUNGUR, Auteur ; Rainer K.W. SCHWARTING, Auteur ; Markus WÖHR, Auteur . - p.696-709. Langues : Anglais (eng) in Autism Research > 9-6 (June 2016) . - p.696-709 Mots-clés : animal model  postsynaptic density  neurodevelopmental disorders  autism  communication  ultrasonic vocalization  social context Index. décimale : PER Périodiques Résumé : Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation-induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1−/− null mutant, Shank1+/− heterozygous, and Shank1+/+ wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD-related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1−/− pups vocalized less and displayed a delay in the typical inverted U-shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype-dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696–709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1564 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=290

Myt1l haploinsufficiency leads to obesity and multifaceted behavioral alterations in mice / Markus WÖHR in Molecular Autism, 13 (2022)  

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