Altered Brain Structure in an ATRX-Deficient Mouse Model of Autism Spectrum Disorder / Katherine QUESNEL in Autism Research, 19-4 (April 2026)  

Public ISBD [article]  inAutism Research > 19-4 (April 2026) . - e70205 Titre : Altered Brain Structure in an ATRX-Deficient Mouse Model of Autism Spectrum Disorder Type de document : texte imprimé Auteurs : Katherine QUESNEL, Auteur ; Jacob ELLEGOOD, Auteur ; Jason P. LERCH, Auteur ; Nathalie G. BÉRUBÉ, Auteur Article en page(s) : e70205 Langues : Anglais (eng) Mots-clés : autism  brain structure  imaging  mice  sex differences Index. décimale : PER Périodiques Résumé : ABSTRACT Mutations in the ATRX gene are a primary cause of alpha-thalassemia intellectual disability X-linked (ATRX) syndrome, which is characterized by intellectual disability, autism, and a range of brain structural abnormalities, including microcephaly. We previously showed that mice with conditional ATRX ablation in forebrain excitatory neurons display deficits in fear memory and autism-related behaviors, with some effects exhibiting sexual dimorphism. In this study, we used high-resolution magnetic resonance imaging (MRI) to systematically characterize brain structural changes associated with these behavioral abnormalities. Whole-brain analysis revealed male-specific microcephaly, while subregional analysis identified significant reductions in hippocampal structures and increased volume of the caudal cortex in mutant animals of both sexes. We also identified structural alterations in regions retaining ATRX expression, such as the thalamus, midbrain, cerebellum, and several fiber tracts. These findings suggest that ATRX loss disrupts the coordinated development of interconnected brain regions. Overall, our results implicate impaired cortico-thalamic-cerebellar connectivity as a potential neural substrate underlying the autistic-like behaviors observed in this mouse model, providing new insights into the neurobiological basis of ATR-X syndrome. En ligne : https://doi.org/10.1002/aur.70205 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=585 [article] Altered Brain Structure in an ATRX-Deficient Mouse Model of Autism Spectrum Disorder [texte imprimé] / Katherine QUESNEL, Auteur ; Jacob ELLEGOOD, Auteur ; Jason P. LERCH, Auteur ; Nathalie G. BÉRUBÉ, Auteur . - e70205. Langues : Anglais (eng) in Autism Research > 19-4 (April 2026) . - e70205 Mots-clés : autism  brain structure  imaging  mice  sex differences Index. décimale : PER Périodiques Résumé : ABSTRACT Mutations in the ATRX gene are a primary cause of alpha-thalassemia intellectual disability X-linked (ATRX) syndrome, which is characterized by intellectual disability, autism, and a range of brain structural abnormalities, including microcephaly. We previously showed that mice with conditional ATRX ablation in forebrain excitatory neurons display deficits in fear memory and autism-related behaviors, with some effects exhibiting sexual dimorphism. In this study, we used high-resolution magnetic resonance imaging (MRI) to systematically characterize brain structural changes associated with these behavioral abnormalities. Whole-brain analysis revealed male-specific microcephaly, while subregional analysis identified significant reductions in hippocampal structures and increased volume of the caudal cortex in mutant animals of both sexes. We also identified structural alterations in regions retaining ATRX expression, such as the thalamus, midbrain, cerebellum, and several fiber tracts. These findings suggest that ATRX loss disrupts the coordinated development of interconnected brain regions. Overall, our results implicate impaired cortico-thalamic-cerebellar connectivity as a potential neural substrate underlying the autistic-like behaviors observed in this mouse model, providing new insights into the neurobiological basis of ATR-X syndrome. En ligne : https://doi.org/10.1002/aur.70205 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=585

Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice / Nicole MARTIN-KENNY in Journal of Neurodevelopmental Disorders, 12 (2020)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 12 (2020) Titre : Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice Type de document : texte imprimé Auteurs : Nicole MARTIN-KENNY, Auteur ; Nathalie G. BÉRUBÉ, Auteur Langues : Anglais (eng) Mots-clés : Animals  Autistic Disorder/genetics  Chromatin Assembly and Disassembly  Female  Male  X-Linked Intellectual Disability/genetics  Mice  Mice, Knockout  Mutation  Neurons/metabolism  Postpartum Period  X-linked Nuclear Protein  alpha-Thalassemia/genetics  Atrx  Autism spectrum disorder  Cre/loxP system  Genetically engineered mice  Repetitive behaviours  Social behaviours  Startle response Index. décimale : PER Périodiques Résumé : BACKGROUND: Alpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations of ATRX result in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by which ATRX mutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatal Atrx inactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours. METHODS: Male and female mice with a postnatal conditional ablation of ATRX were generated using the Cre/lox system under the control of the αCaMKII gene promoter. These mice were tested in a battery of behavioural tests that assess autistic-like features. We utilized paradigms that measure social behaviour, repetitive, and stereotyped behaviours, as well as sensory gating. Statistics were calculated by two-way repeated measures ANOVA with Sidak's multiple comparison test or unpaired Student's t tests as indicated. RESULTS: The behaviour tests revealed no significant differences between Atrx-cKO and control mice. We identified sexually dimorphic changes in odor habituation and discrimination; however, these changes did not correlate with social deficits. CONCLUSION: The postnatal knockout of Atrx in forebrain excitatory neurons does not lead to autism-related behaviours in male or female mice. En ligne : https://dx.doi.org/10.1186/s11689-020-09319-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573 [article] Effects of a postnatal Atrx conditional knockout in neurons on autism-like behaviours in male and female mice [texte imprimé] / Nicole MARTIN-KENNY, Auteur ; Nathalie G. BÉRUBÉ, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 12 (2020) Mots-clés : Animals  Autistic Disorder/genetics  Chromatin Assembly and Disassembly  Female  Male  X-Linked Intellectual Disability/genetics  Mice  Mice, Knockout  Mutation  Neurons/metabolism  Postpartum Period  X-linked Nuclear Protein  alpha-Thalassemia/genetics  Atrx  Autism spectrum disorder  Cre/loxP system  Genetically engineered mice  Repetitive behaviours  Social behaviours  Startle response Index. décimale : PER Périodiques Résumé : BACKGROUND: Alpha-thalassemia/mental retardation, X-linked, or ATRX, is an autism susceptibility gene that encodes a chromatin remodeler. Mutations of ATRX result in the ATR-X intellectual disability syndrome and have been identified in autism spectrum disorder (ASD) patients. The mechanisms by which ATRX mutations lead to autism and autistic-like behaviours are not yet known. To address this question, we generated mice with postnatal Atrx inactivation in excitatory neurons of the forebrain and performed a battery of behavioural assays that assess autistic-like behaviours. METHODS: Male and female mice with a postnatal conditional ablation of ATRX were generated using the Cre/lox system under the control of the αCaMKII gene promoter. These mice were tested in a battery of behavioural tests that assess autistic-like features. We utilized paradigms that measure social behaviour, repetitive, and stereotyped behaviours, as well as sensory gating. Statistics were calculated by two-way repeated measures ANOVA with Sidak's multiple comparison test or unpaired Student's t tests as indicated. RESULTS: The behaviour tests revealed no significant differences between Atrx-cKO and control mice. We identified sexually dimorphic changes in odor habituation and discrimination; however, these changes did not correlate with social deficits. CONCLUSION: The postnatal knockout of Atrx in forebrain excitatory neurons does not lead to autism-related behaviours in male or female mice. En ligne : https://dx.doi.org/10.1186/s11689-020-09319-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=573

A mouse model of ATRX deficiency with cognitive deficits and autistic traits / Katherine M. QUESNEL in Journal of Neurodevelopmental Disorders, 15 (2023)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 15 (2023) Titre : A mouse model of ATRX deficiency with cognitive deficits and autistic traits Type de document : texte imprimé Auteurs : Katherine M. QUESNEL, Auteur ; Nicole MARTIN-KENNY, Auteur ; Nathalie G. BÉRUBÉ, Auteur Langues : Anglais (eng) Mots-clés : Male  Cognition  X-Linked Intellectual Disability  Neurons/physiology  Memory Disorders/etiology  Female  alpha-Thalassemia  Autistic Disorder/complications/genetics  Mice  Animals  Atrx  Autism  Intellectual disability  Sex differences Index. décimale : PER Périodiques Résumé : BACKGROUND: ATRX is an ATP-dependent chromatin remodeling protein with essential roles in safeguarding genome integrity and modulating gene expression. Deficiencies in this protein cause ATR-X syndrome, a condition characterized by intellectual disability and an array of developmental abnormalities, including features of autism. Previous studies demonstrated that deleting ATRX in mouse forebrain excitatory neurons postnatally resulted in male-specific memory deficits, but no apparent autistic-like behaviours. METHODS: We generated mice with an earlier embryonic deletion of ATRX in forebrain excitatory neurons and characterized their behaviour using a series of memory and autistic-related paradigms. RESULTS: We found that mutant mice displayed a broader spectrum of impairments, including fear memory, decreased anxiety-like behaviour, hyperactivity, as well as self-injurious and repetitive grooming. Sex-specific alterations were also observed, including male-specific aggression, sensory gating impairments, and decreased social memory. CONCLUSIONS: Collectively, the findings indicate that early developmental abnormalities arising from ATRX deficiency in forebrain excitatory neurons contribute to the presentation of fear memory deficits as well as autistic-like behaviours. En ligne : https://dx.doi.org/10.1186/s11689-023-09508-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575 [article] A mouse model of ATRX deficiency with cognitive deficits and autistic traits [texte imprimé] / Katherine M. QUESNEL, Auteur ; Nicole MARTIN-KENNY, Auteur ; Nathalie G. BÉRUBÉ, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 15 (2023) Mots-clés : Male  Cognition  X-Linked Intellectual Disability  Neurons/physiology  Memory Disorders/etiology  Female  alpha-Thalassemia  Autistic Disorder/complications/genetics  Mice  Animals  Atrx  Autism  Intellectual disability  Sex differences Index. décimale : PER Périodiques Résumé : BACKGROUND: ATRX is an ATP-dependent chromatin remodeling protein with essential roles in safeguarding genome integrity and modulating gene expression. Deficiencies in this protein cause ATR-X syndrome, a condition characterized by intellectual disability and an array of developmental abnormalities, including features of autism. Previous studies demonstrated that deleting ATRX in mouse forebrain excitatory neurons postnatally resulted in male-specific memory deficits, but no apparent autistic-like behaviours. METHODS: We generated mice with an earlier embryonic deletion of ATRX in forebrain excitatory neurons and characterized their behaviour using a series of memory and autistic-related paradigms. RESULTS: We found that mutant mice displayed a broader spectrum of impairments, including fear memory, decreased anxiety-like behaviour, hyperactivity, as well as self-injurious and repetitive grooming. Sex-specific alterations were also observed, including male-specific aggression, sensory gating impairments, and decreased social memory. CONCLUSIONS: Collectively, the findings indicate that early developmental abnormalities arising from ATRX deficiency in forebrain excitatory neurons contribute to the presentation of fear memory deficits as well as autistic-like behaviours. En ligne : https://dx.doi.org/10.1186/s11689-023-09508-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=575

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