4 recherche sur le mot-clé 'phenotyping'

Autism-like phenotype across the lifespan of Shank3B-mutant mice of both sexes / Jakub SZABÓ in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : Autism-like phenotype across the lifespan of Shank3B-mutant mice of both sexes Type de document : texte imprimé Auteurs : Jakub SZABÓ, Auteur ; Johan FILO, Auteur ; Rebeka DÉMUTHOVÁ, Auteur ; Emese RENCZÉS, Auteur ; Veronika BORBÉLYOVÁ, Auteur ; Daniela OSTATNIKOVA, Auteur ; Peter CELEC, Auteur Langues : Anglais (eng) Mots-clés : Animals  Male  Female  Mice  Nerve Tissue Proteins/genetics  Behavior, Animal/physiology  Phenotype  Disease Models, Animal  Mice, Inbred C57BL  Autism Spectrum Disorder/genetics/physiopathology  Anxiety/genetics/physiopathology  Aging/physiology  Social Behavior  Mice, Knockout  Sex Factors  Microfilament Proteins  Animal model  Phelan-McDermid syndrome  Phenotyping  Symptom development  conducted in accordance with the Slovak national laws and approved by the ethics  committee of the Institute of Molecular Biomedicine. Consent for publication: Not  applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: High heritability (80-90%) of the autism spectrum disorder (ASD) and sex-biased incidence (3-4 times more boys than girls) suggest the roles of genetic predisposition and sex in the etiopathogenesis of the disorder. As ASD is commonly diagnosed in early childhood, most of the research is focused on children, yet animal research predominantly uses adult-aged animals. The effect of aging on the core and secondary ASD symptomatology is understudied, both in patients and animal models of ASD. METHODS: To investigate the effect of aging on sociability, repetitive behavior, exploration, locomotor activity, anxiety-like behavior, and object-avoidance behavior, behavioral phenotyping was conducted in Shank3B(-/-) (n = 67) and C57BL/6J wild-type (WT, n = 68) mice of both sexes (female n = 70, male n = 65) in adolescence (1-2 months of age, n = 42), adulthood (3-6 months of age, n = 40), and old age (12-18 months of age, n = 53). RESULTS: Social deficits were observed only in old Shank3B(-/-) males. Anxiety-like behavior peaked in adulthood with Shank3B(-/-) mice roughly 20% more anxious than controls. Repetitive grooming and object-induced avoidance behavior were twice more prevalent in Shank3B(-/-) mice consistently across the lifespan. Hypoactivity (20% less distance moved) and reduced exploration (30% less rearing behavior) were recorded in Shank3B(-/-) mice and were more prevalent in female animals (30% less rearing behavior). Data were analyzed using the Three-way ANOVA (genotype, sex, age), followed by a posthoc Bonferroni correction to compare respective subgroups. CONCLUSIONS: Present study shows that aging affects ASD-like phenotype in the Shank3B-mutant mouse model, even though the effect size seems to be small. The mechanisms underlying these partially sex-specific effects should be the subject of further research with potential translational implications. En ligne : https://dx.doi.org/10.1186/s11689-025-09635-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Autism-like phenotype across the lifespan of Shank3B-mutant mice of both sexes [texte imprimé] / Jakub SZABÓ, Auteur ; Johan FILO, Auteur ; Rebeka DÉMUTHOVÁ, Auteur ; Emese RENCZÉS, Auteur ; Veronika BORBÉLYOVÁ, Auteur ; Daniela OSTATNIKOVA, Auteur ; Peter CELEC, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Animals  Male  Female  Mice  Nerve Tissue Proteins/genetics  Behavior, Animal/physiology  Phenotype  Disease Models, Animal  Mice, Inbred C57BL  Autism Spectrum Disorder/genetics/physiopathology  Anxiety/genetics/physiopathology  Aging/physiology  Social Behavior  Mice, Knockout  Sex Factors  Microfilament Proteins  Animal model  Phelan-McDermid syndrome  Phenotyping  Symptom development  conducted in accordance with the Slovak national laws and approved by the ethics  committee of the Institute of Molecular Biomedicine. Consent for publication: Not  applicable. Competing interests: The authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: High heritability (80-90%) of the autism spectrum disorder (ASD) and sex-biased incidence (3-4 times more boys than girls) suggest the roles of genetic predisposition and sex in the etiopathogenesis of the disorder. As ASD is commonly diagnosed in early childhood, most of the research is focused on children, yet animal research predominantly uses adult-aged animals. The effect of aging on the core and secondary ASD symptomatology is understudied, both in patients and animal models of ASD. METHODS: To investigate the effect of aging on sociability, repetitive behavior, exploration, locomotor activity, anxiety-like behavior, and object-avoidance behavior, behavioral phenotyping was conducted in Shank3B(-/-) (n = 67) and C57BL/6J wild-type (WT, n = 68) mice of both sexes (female n = 70, male n = 65) in adolescence (1-2 months of age, n = 42), adulthood (3-6 months of age, n = 40), and old age (12-18 months of age, n = 53). RESULTS: Social deficits were observed only in old Shank3B(-/-) males. Anxiety-like behavior peaked in adulthood with Shank3B(-/-) mice roughly 20% more anxious than controls. Repetitive grooming and object-induced avoidance behavior were twice more prevalent in Shank3B(-/-) mice consistently across the lifespan. Hypoactivity (20% less distance moved) and reduced exploration (30% less rearing behavior) were recorded in Shank3B(-/-) mice and were more prevalent in female animals (30% less rearing behavior). Data were analyzed using the Three-way ANOVA (genotype, sex, age), followed by a posthoc Bonferroni correction to compare respective subgroups. CONCLUSIONS: Present study shows that aging affects ASD-like phenotype in the Shank3B-mutant mouse model, even though the effect size seems to be small. The mechanisms underlying these partially sex-specific effects should be the subject of further research with potential translational implications. En ligne : https://dx.doi.org/10.1186/s11689-025-09635-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Genetic mouse models of autism spectrum disorder present subtle heterogenous cardiac abnormalities / Stephania ASSIMOPOULOS in Autism Research, 15-7 (July 2022)  

Public ISBD [article]  inAutism Research > 15-7 (July 2022) . - p.1189-1208 Titre : Genetic mouse models of autism spectrum disorder present subtle heterogenous cardiac abnormalities Type de document : texte imprimé Auteurs : Stephania ASSIMOPOULOS, Auteur ; Christopher HAMMILL, Auteur ; Darren J. FERNANDES, Auteur ; Tara LEIGH SPENCER NOAKES, Auteur ; Yu-Qing ZHOU, Auteur ; Lauryl M J. NUTTER, Auteur ; Jacob ELLEGOOD, Auteur ; Evdokia ANAGNOSTOU, Auteur ; John G. SLED, Auteur ; Jason P. LERCH, Auteur Article en page(s) : p.1189-1208 Langues : Anglais (eng) Mots-clés : autism  cardiac phenotype/cardiology  comorbidities  genetic mouse models  phenotyping  ultrasound biomicroscopy Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) and congenital heart disease (CHD) are linked on a functional and genetic level. Most work has investigated CHD-related neurodevelopmental abnormalities. Cardiac abnormalities in ASD have been less studied. We investigated the prevalence of cardiac comorbidities relative to ASD genetic contributors. Using high frequency ultrasound imaging, we screened 9 ASD-related genetic mouse models (Arid1b((+/-)) , Chd8((+/-)) , 16p11.2 (deletion), Sgsh((+/-)) , Sgsh((-/-)) , Shank3 ?exon 4-9((+/-)) , Shank3 ?exon 4-9((-/-)) , Fmr1((-/-)) , Vps13b((+/-)) ), and pooled wild-type littermates (WTs). We measured heart rate (HR), aorta diameter (AoD), thickness and thickening of the left-ventricular (LV) anterior and posterior walls, LV chamber diameter, fractional shortening, stroke volume and cardiac output, mitral inflow Peak E and A velocity ratio, ascending aorta velocity time integral (VTI). Mutant groups presented small-scale alterations in cardiac structure and function compared to WTs (LV anterior wall thickness and thickening, chamber diameter and fractional shortening, HR). A greater number of significant differences was observed among mutant groups than between mutant groups and WTs. Mutant groups differed primarily in structural measures (LV chamber diameter and anterior wall thickness, HR, AoD). The mutant groups with most differences to WTs were 16p11.2 (deletion), Fmr1((-/-)) , Arid1b((+/-)) . The mutant groups with most differences from other mutant groups were 16p11.2 (deletion), Sgsh((+/-)) , Fmr1((-/-)) . Our results recapitulate the associated clinical findings. The characteristic ASD heterogeneity was recapitulated in the cardiac phenotype. The type of abnormal measures (morphological, functional) can highlight common underlying mechanisms. Clinically, knowledge of cardiac abnormalities in ASD can be essential as even non-lethal abnormalities impact normal development. LAY SUMMARY: Autism spectrum disorder (ASD) and congenital heart disease (CHD) are linked functionally and genetically. ASD cardiac phenotyping is limited. We assessed the cardiac phenotype of 9 ASD-related mouse models. We found subtle heterogenous cardiac abnormalities compared to controls, with more differences within ASD than between ASD and controls, mirroring clinical findings. Clinically, knowing the cardiac abnormalities in ASD is vital as even non-lethal cardiac abnormalities can impact development. En ligne : http://dx.doi.org/10.1002/aur.2728 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476 [article] Genetic mouse models of autism spectrum disorder present subtle heterogenous cardiac abnormalities [texte imprimé] / Stephania ASSIMOPOULOS, Auteur ; Christopher HAMMILL, Auteur ; Darren J. FERNANDES, Auteur ; Tara LEIGH SPENCER NOAKES, Auteur ; Yu-Qing ZHOU, Auteur ; Lauryl M J. NUTTER, Auteur ; Jacob ELLEGOOD, Auteur ; Evdokia ANAGNOSTOU, Auteur ; John G. SLED, Auteur ; Jason P. LERCH, Auteur . - p.1189-1208. Langues : Anglais (eng) in Autism Research > 15-7 (July 2022) . - p.1189-1208 Mots-clés : autism  cardiac phenotype/cardiology  comorbidities  genetic mouse models  phenotyping  ultrasound biomicroscopy Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) and congenital heart disease (CHD) are linked on a functional and genetic level. Most work has investigated CHD-related neurodevelopmental abnormalities. Cardiac abnormalities in ASD have been less studied. We investigated the prevalence of cardiac comorbidities relative to ASD genetic contributors. Using high frequency ultrasound imaging, we screened 9 ASD-related genetic mouse models (Arid1b((+/-)) , Chd8((+/-)) , 16p11.2 (deletion), Sgsh((+/-)) , Sgsh((-/-)) , Shank3 ?exon 4-9((+/-)) , Shank3 ?exon 4-9((-/-)) , Fmr1((-/-)) , Vps13b((+/-)) ), and pooled wild-type littermates (WTs). We measured heart rate (HR), aorta diameter (AoD), thickness and thickening of the left-ventricular (LV) anterior and posterior walls, LV chamber diameter, fractional shortening, stroke volume and cardiac output, mitral inflow Peak E and A velocity ratio, ascending aorta velocity time integral (VTI). Mutant groups presented small-scale alterations in cardiac structure and function compared to WTs (LV anterior wall thickness and thickening, chamber diameter and fractional shortening, HR). A greater number of significant differences was observed among mutant groups than between mutant groups and WTs. Mutant groups differed primarily in structural measures (LV chamber diameter and anterior wall thickness, HR, AoD). The mutant groups with most differences to WTs were 16p11.2 (deletion), Fmr1((-/-)) , Arid1b((+/-)) . The mutant groups with most differences from other mutant groups were 16p11.2 (deletion), Sgsh((+/-)) , Fmr1((-/-)) . Our results recapitulate the associated clinical findings. The characteristic ASD heterogeneity was recapitulated in the cardiac phenotype. The type of abnormal measures (morphological, functional) can highlight common underlying mechanisms. Clinically, knowledge of cardiac abnormalities in ASD can be essential as even non-lethal abnormalities impact normal development. LAY SUMMARY: Autism spectrum disorder (ASD) and congenital heart disease (CHD) are linked functionally and genetically. ASD cardiac phenotyping is limited. We assessed the cardiac phenotype of 9 ASD-related mouse models. We found subtle heterogenous cardiac abnormalities compared to controls, with more differences within ASD than between ASD and controls, mirroring clinical findings. Clinically, knowing the cardiac abnormalities in ASD is vital as even non-lethal cardiac abnormalities can impact development. En ligne : http://dx.doi.org/10.1002/aur.2728 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476

Genetic Variation in Melatonin Pathway Enzymes in Children with Autism Spectrum Disorder and Comorbid Sleep Onset Delay / Olivia J. VEATCH in Journal of Autism and Developmental Disorders, 45-1 (January 2015)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 45-1 (January 2015) . - p.100-110 Titre : Genetic Variation in Melatonin Pathway Enzymes in Children with Autism Spectrum Disorder and Comorbid Sleep Onset Delay Type de document : texte imprimé Auteurs : Olivia J. VEATCH, Auteur ; Julie S. PENDERGAST, Auteur ; Melissa J. ALLEN, Auteur ; Roberta M. LEU, Auteur ; Carl Hirschie JOHNSON, Auteur ; Sarah H. ELSEA, Auteur ; Beth A. MALOW, Auteur Article en page(s) : p.100-110 Langues : Anglais (eng) Mots-clés : Comorbidities  Genetic analyses  Phenotyping  Phenotypic subgroups  Biomarkers  Endophenotypes Index. décimale : PER Périodiques Résumé : Sleep disruption is common in individuals with autism spectrum disorder (ASD). Genes whose products regulate endogenous melatonin modify sleep patterns and have been implicated in ASD. Genetic factors likely contribute to comorbid expression of sleep disorders in ASD. We studied a clinically unique ASD subgroup, consisting solely of children with comorbid expression of sleep onset delay. We evaluated variation in two melatonin pathway genes, acetylserotonin O-methyltransferase (ASMT) and cytochrome P450 1A2 (CYP1A2). We observed higher frequencies than currently reported (p < 0.04) for variants evidenced to decrease ASMT expression and related to decreased CYP1A2 enzyme activity (p ≤ 0.0007). We detected a relationship between genotypes in ASMT and CYP1A2 (r2 = 0.63). Our results indicate that expression of sleep onset delay relates to melatonin pathway genes. En ligne : http://dx.doi.org/10.1007/s10803-014-2197-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=258 [article] Genetic Variation in Melatonin Pathway Enzymes in Children with Autism Spectrum Disorder and Comorbid Sleep Onset Delay [texte imprimé] / Olivia J. VEATCH, Auteur ; Julie S. PENDERGAST, Auteur ; Melissa J. ALLEN, Auteur ; Roberta M. LEU, Auteur ; Carl Hirschie JOHNSON, Auteur ; Sarah H. ELSEA, Auteur ; Beth A. MALOW, Auteur . - p.100-110. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 45-1 (January 2015) . - p.100-110 Mots-clés : Comorbidities  Genetic analyses  Phenotyping  Phenotypic subgroups  Biomarkers  Endophenotypes Index. décimale : PER Périodiques Résumé : Sleep disruption is common in individuals with autism spectrum disorder (ASD). Genes whose products regulate endogenous melatonin modify sleep patterns and have been implicated in ASD. Genetic factors likely contribute to comorbid expression of sleep disorders in ASD. We studied a clinically unique ASD subgroup, consisting solely of children with comorbid expression of sleep onset delay. We evaluated variation in two melatonin pathway genes, acetylserotonin O-methyltransferase (ASMT) and cytochrome P450 1A2 (CYP1A2). We observed higher frequencies than currently reported (p < 0.04) for variants evidenced to decrease ASMT expression and related to decreased CYP1A2 enzyme activity (p ≤ 0.0007). We detected a relationship between genotypes in ASMT and CYP1A2 (r2 = 0.63). Our results indicate that expression of sleep onset delay relates to melatonin pathway genes. En ligne : http://dx.doi.org/10.1007/s10803-014-2197-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=258

Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions / Emily NEUHAUS in Journal of Neurodevelopmental Disorders, 16 (2024)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 16 (2024) Titre : Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions Type de document : texte imprimé Auteurs : Emily NEUHAUS, Auteur ; Hannah REA, Auteur ; Elizabeth JONES, Auteur ; Hannah BENAVIDEZ, Auteur ; Conor MILES, Auteur ; Alana WHITING, Auteur ; Margaret JOHANSSON, Auteur ; Curtis EAYRS, Auteur ; Evangeline C. KURTZ-NELSON, Auteur ; Rachel EARL, Auteur ; Raphael A. BERNIER, Auteur ; Evan E. EICHLER, Auteur Langues : Anglais (eng) Mots-clés : Adolescent  Child  Female  Humans  Male  Autism Spectrum Disorder/complications  DNA-Binding Proteins/genetics  Homeodomain Proteins/genetics  Intellectual Disability/genetics/complications  Mental Health  Nerve Tissue Proteins/genetics  Neurodevelopmental Disorders/genetics/complications  Quality of Life  Transcription Factors/genetics  Adnp  Chd8  Dyrk1a  Asd  Autism  Neurodevelopmental conditions  Phenotyping  genetics  opinions or views of the National Institutes of Health (NIH). E.E.E. is a  scientific advisory board (SAB) member of Variant Bio, Inc. The remaining authors  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD - ADNP, CHD8, and DYRK1A - with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes. METHODS: Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features. RESULTS: Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group. CONCLUSIONS: Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life. En ligne : https://dx.doi.org/10.1186/s11689-024-09532-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] Shared and divergent mental health characteristics of ADNP-, CHD8- and DYRK1A-related neurodevelopmental conditions [texte imprimé] / Emily NEUHAUS, Auteur ; Hannah REA, Auteur ; Elizabeth JONES, Auteur ; Hannah BENAVIDEZ, Auteur ; Conor MILES, Auteur ; Alana WHITING, Auteur ; Margaret JOHANSSON, Auteur ; Curtis EAYRS, Auteur ; Evangeline C. KURTZ-NELSON, Auteur ; Rachel EARL, Auteur ; Raphael A. BERNIER, Auteur ; Evan E. EICHLER, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 16 (2024) Mots-clés : Adolescent  Child  Female  Humans  Male  Autism Spectrum Disorder/complications  DNA-Binding Proteins/genetics  Homeodomain Proteins/genetics  Intellectual Disability/genetics/complications  Mental Health  Nerve Tissue Proteins/genetics  Neurodevelopmental Disorders/genetics/complications  Quality of Life  Transcription Factors/genetics  Adnp  Chd8  Dyrk1a  Asd  Autism  Neurodevelopmental conditions  Phenotyping  genetics  opinions or views of the National Institutes of Health (NIH). E.E.E. is a  scientific advisory board (SAB) member of Variant Bio, Inc. The remaining authors  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental conditions such as intellectual disability (ID) and autism spectrum disorder (ASD) can stem from a broad array of inherited and de novo genetic differences, with marked physiological and behavioral impacts. We currently know little about the psychiatric phenotypes of rare genetic variants associated with ASD, despite heightened risk of psychiatric concerns in ASD more broadly. Understanding behavioral features of these variants can identify shared versus specific phenotypes across gene groups, facilitate mechanistic models, and provide prognostic insights to inform clinical practice. In this paper, we evaluate behavioral features within three gene groups associated with ID and ASD - ADNP, CHD8, and DYRK1A - with two aims: (1) characterize phenotypes across behavioral domains of anxiety, depression, ADHD, and challenging behavior; and (2) understand whether age and early developmental milestones are associated with later mental health outcomes. METHODS: Phenotypic data were obtained for youth with disruptive variants in ADNP, CHD8, or DYRK1A (N = 65, mean age = 8.7 years, 40% female) within a long-running, genetics-first study. Standardized caregiver-report measures of mental health features (anxiety, depression, attention-deficit/hyperactivity, oppositional behavior) and developmental history were extracted and analyzed for effects of gene group, age, and early developmental milestones on mental health features. RESULTS: Patterns of mental health features varied by group, with anxiety most prominent for CHD8, oppositional features overrepresented among ADNP, and attentional and depressive features most prominent for DYRK1A. For the full sample, age was positively associated with anxiety features, such that elevations in anxiety relative to same-age and same-sex peers may worsen with increasing age. Predictive utility of early developmental milestones was limited, with evidence of early language delays predicting greater difficulties across behavioral domains only for the CHD8 group. CONCLUSIONS: Despite shared associations with autism and intellectual disability, disruptive variants in ADNP, CHD8, and DYRK1A may yield variable psychiatric phenotypes among children and adolescents. With replication in larger samples over time, efforts such as these may contribute to improved clinical care for affected children and adolescents, allow for earlier identification of emerging mental health difficulties, and promote early intervention to alleviate concerns and improve quality of life. En ligne : https://dx.doi.org/10.1186/s11689-024-09532-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575