22 recherche sur le mot-clé 'Mice, Knockout'

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

Tau reduction attenuates autism-like features in Fmr1 knockout mice / Xiangyu JIANG ; Linkun HAN ; Yiru JIANG ; Yong WANG ; Jian MENG ; Xiang ZHU ; Xian ZHANG ; Hong LUO ; Yun-Wu ZHANG in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 42 p. Titre : Tau reduction attenuates autism-like features in Fmr1 knockout mice Type de document : texte imprimé Auteurs : Xiangyu JIANG, Auteur ; Linkun HAN, Auteur ; Yiru JIANG, Auteur ; Yong WANG, Auteur ; Jian MENG, Auteur ; Xiang ZHU, Auteur ; Xian ZHANG, Auteur ; Hong LUO, Auteur ; Yun-Wu ZHANG, Auteur Article en page(s) : 42 p. Langues : Anglais (eng) Mots-clés : Animals  Mice  Male  Female  Mice, Knockout  *Autism Spectrum Disorder  *Autistic Disorder/genetics  tau Proteins/genetics/metabolism  Fragile X Mental Retardation Protein/genetics/metabolism  *Fragile X Syndrome/genetics/metabolism  Disease Models, Animal  Antisense oligonucleotide  Autism spectrum disorder  Fmr1  Fragile X syndrome  P38/MAPK signaling  Tau Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. However, whether Tau reduction can prevent autism-like features in Fmr1 KO mice and become a novel strategy for FXS treatment remain unknown. METHODS: Tau was genetically reduced in Fmr1 KO mice through crossing Fmr1(+) female mice with Mapt(+) male mice. The male offspring with different genotypes were subjected to various autism-related behavioral tests, RNA sequencing, and biochemical analysis. Fmr1 KO male mice were treated with Tau-targeting antisense oligonucleotide (ASO) and then subjected to behavioral tests and biochemical analysis. RESULTS: Tau expression was increased in the cortex of Fmr1 KO mice. Genetically reducing Tau prevented social defects, stereotyped and repetitive behavior, and spine abnormality in Fmr1 KO mice. Tau reduction also reversed increased periodic activity and partially rescued Per1 expression reduction in Fmr1 KO mice. Moreover, Tau reduction reversed compromised P38/MAPK signaling in Fmr1 KO mice. Finally, Tau-targeting ASO also effectively alleviated autism-like phenotypes and promoted P38/MAPK signaling in Fmr1 KO mice. LIMITATIONS: Our study is limited to male mice, in agreement with the higher incidence of FXS in males than females. Whether Tau reduction also exerts protection in females deserves further scrutiny. Moreover, although Tau reduction rescues impaired P38/MAPK signaling in Fmr1 KO mice, whether this is the responsible molecular mechanism requires further determination. CONCLUSION: Our data indicate that Tau reduction prevents autism-like phenotypes in Fmr1 KO mice. Tau may become a new target for FXS treatment. En ligne : https://dx.doi.org/10.1186/s13229-023-00574-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518 [article] Tau reduction attenuates autism-like features in Fmr1 knockout mice [texte imprimé] / Xiangyu JIANG, Auteur ; Linkun HAN, Auteur ; Yiru JIANG, Auteur ; Yong WANG, Auteur ; Jian MENG, Auteur ; Xiang ZHU, Auteur ; Xian ZHANG, Auteur ; Hong LUO, Auteur ; Yun-Wu ZHANG, Auteur . - 42 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 42 p. Mots-clés : Animals  Mice  Male  Female  Mice, Knockout  *Autism Spectrum Disorder  *Autistic Disorder/genetics  tau Proteins/genetics/metabolism  Fragile X Mental Retardation Protein/genetics/metabolism  *Fragile X Syndrome/genetics/metabolism  Disease Models, Animal  Antisense oligonucleotide  Autism spectrum disorder  Fmr1  Fragile X syndrome  P38/MAPK signaling  Tau Index. décimale : PER Périodiques Résumé : BACKGROUND: Fragile X syndrome (FXS) is a leading cause of autism spectrum disorder (ASD) and resulted from a loss of the FMR1-encoded fragile X messenger ribonucleoprotein 1 (FMRP) protein due to large CGG repeat expansions in the promoter region of the FMR1 gene. The microtubule-associated protein Tau is a promising target for Tauopathic diseases and our preliminary study found that Tau protein levels were increased in the brain of Fmr1 knockout (KO) mice, a model of FXS. However, whether Tau reduction can prevent autism-like features in Fmr1 KO mice and become a novel strategy for FXS treatment remain unknown. METHODS: Tau was genetically reduced in Fmr1 KO mice through crossing Fmr1(+) female mice with Mapt(+) male mice. The male offspring with different genotypes were subjected to various autism-related behavioral tests, RNA sequencing, and biochemical analysis. Fmr1 KO male mice were treated with Tau-targeting antisense oligonucleotide (ASO) and then subjected to behavioral tests and biochemical analysis. RESULTS: Tau expression was increased in the cortex of Fmr1 KO mice. Genetically reducing Tau prevented social defects, stereotyped and repetitive behavior, and spine abnormality in Fmr1 KO mice. Tau reduction also reversed increased periodic activity and partially rescued Per1 expression reduction in Fmr1 KO mice. Moreover, Tau reduction reversed compromised P38/MAPK signaling in Fmr1 KO mice. Finally, Tau-targeting ASO also effectively alleviated autism-like phenotypes and promoted P38/MAPK signaling in Fmr1 KO mice. LIMITATIONS: Our study is limited to male mice, in agreement with the higher incidence of FXS in males than females. Whether Tau reduction also exerts protection in females deserves further scrutiny. Moreover, although Tau reduction rescues impaired P38/MAPK signaling in Fmr1 KO mice, whether this is the responsible molecular mechanism requires further determination. CONCLUSION: Our data indicate that Tau reduction prevents autism-like phenotypes in Fmr1 KO mice. Tau may become a new target for FXS treatment. En ligne : https://dx.doi.org/10.1186/s13229-023-00574-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=518

Enhanced fear limits behavioral flexibility in Shank2-deficient mice / Miru YUN in Molecular Autism, 13 (2022)  

Public ISBD [article]  inMolecular Autism > 13 (2022) . - 40 p. Titre : Enhanced fear limits behavioral flexibility in Shank2-deficient mice Type de document : texte imprimé Auteurs : Miru YUN, Auteur ; Eunjoon KIM, Auteur ; Min Whan JUNG, Auteur Article en page(s) : 40 p. Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/genetics/psychology  Conditioning, Classical  Disease Models, Animal  Fear  Male  Mice  Mice, Knockout  Nerve Tissue Proteins/genetics  Water  Classical conditioning  Reversal learning  Shank2 Index. décimale : PER Périodiques Résumé : BACKGROUND: A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and restrictive behavior in ASD. Here, we investigated whether and how behavioral flexibility is compromised in a widely used animal model of ASD. METHODS: We compared the behavioral performance of Shank2-knockout mice and wild-type littermates in reversal learning employing a probabilistic classical trace conditioning paradigm. A conditioned stimulus (odor) was paired with an unconditioned appetitive (water, 6 Âul) or aversive (air puff) stimulus in a probabilistic manner. We also compared air puff-induced eye closure responses of Shank2-knockout and wild-type mice. RESULTS: Male, but not female, Shank2-knockout mice showed impaired reversal learning when the expected outcomes consisted of a water reward and a strong air puff. Moreover, male, but not female, Shank2-knockout mice showed stronger anticipatory eye closure responses to the air puff compared to wild-type littermates, raising the possibility that the impairment might reflect enhanced fear. In support of this contention, male Shank2-knockout mice showed intact reversal learning when the strong air puff was replaced with a mild air puff and when the expected outcomes consisted of only rewards. LIMITATIONS: We examined behavioral flexibility in one behavioral task (reversal learning in a probabilistic classical trace conditioning paradigm) using one ASD mouse model (Shank2-knockout mice). Thus, future work is needed to clarify the extent to which our findings (that enhanced fear limits behavioral flexibility in ASD) can explain the behavioral inflexibility associated with ASD. Also, we examined only the relationship between fear and behavioral flexibility, leaving open the question of whether abnormalities in processes other than fear contribute to behavioral inflexibility in ASD. Finally, the neurobiological mechanisms linking Shank2-knockout and enhanced fear remain to be elucidated. CONCLUSIONS: Our results indicate that enhanced fear suppresses reversal learning in the presence of an intact capability to learn cue-outcome contingency changes in Shank2-knockout mice. Our findings suggest that behavioral flexibility might be seriously limited by abnormal emotional responses in ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00518-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491 [article] Enhanced fear limits behavioral flexibility in Shank2-deficient mice [texte imprimé] / Miru YUN, Auteur ; Eunjoon KIM, Auteur ; Min Whan JUNG, Auteur . - 40 p. Langues : Anglais (eng) in Molecular Autism > 13 (2022) . - 40 p. Mots-clés : Animals  Autism Spectrum Disorder/genetics/psychology  Conditioning, Classical  Disease Models, Animal  Fear  Male  Mice  Mice, Knockout  Nerve Tissue Proteins/genetics  Water  Classical conditioning  Reversal learning  Shank2 Index. décimale : PER Périodiques Résumé : BACKGROUND: A core symptom of autism spectrum disorder (ASD) is repetitive and restrictive patterns of behavior. Cognitive inflexibility has been proposed as a potential basis for these symptoms of ASD. More generally, behavioral inflexibility has been proposed to underlie repetitive and restrictive behavior in ASD. Here, we investigated whether and how behavioral flexibility is compromised in a widely used animal model of ASD. METHODS: We compared the behavioral performance of Shank2-knockout mice and wild-type littermates in reversal learning employing a probabilistic classical trace conditioning paradigm. A conditioned stimulus (odor) was paired with an unconditioned appetitive (water, 6 Âul) or aversive (air puff) stimulus in a probabilistic manner. We also compared air puff-induced eye closure responses of Shank2-knockout and wild-type mice. RESULTS: Male, but not female, Shank2-knockout mice showed impaired reversal learning when the expected outcomes consisted of a water reward and a strong air puff. Moreover, male, but not female, Shank2-knockout mice showed stronger anticipatory eye closure responses to the air puff compared to wild-type littermates, raising the possibility that the impairment might reflect enhanced fear. In support of this contention, male Shank2-knockout mice showed intact reversal learning when the strong air puff was replaced with a mild air puff and when the expected outcomes consisted of only rewards. LIMITATIONS: We examined behavioral flexibility in one behavioral task (reversal learning in a probabilistic classical trace conditioning paradigm) using one ASD mouse model (Shank2-knockout mice). Thus, future work is needed to clarify the extent to which our findings (that enhanced fear limits behavioral flexibility in ASD) can explain the behavioral inflexibility associated with ASD. Also, we examined only the relationship between fear and behavioral flexibility, leaving open the question of whether abnormalities in processes other than fear contribute to behavioral inflexibility in ASD. Finally, the neurobiological mechanisms linking Shank2-knockout and enhanced fear remain to be elucidated. CONCLUSIONS: Our results indicate that enhanced fear suppresses reversal learning in the presence of an intact capability to learn cue-outcome contingency changes in Shank2-knockout mice. Our findings suggest that behavioral flexibility might be seriously limited by abnormal emotional responses in ASD. En ligne : http://dx.doi.org/10.1186/s13229-022-00518-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=491

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

Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density / Susan R. BERKOWICZ in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 22p. Titre : Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density Type de document : texte imprimé Auteurs : Susan R. BERKOWICZ, Auteur ; Travis J. FEATHERBY, Auteur ; Zhengdong QU, Auteur ; Aminah GIOUSOH, Auteur ; Natalie A. BORG, Auteur ; Julian I. HENG, Auteur ; James C. WHISSTOCK, Auteur ; P.I. BIRD, Auteur Article en page(s) : 22p. Langues : Anglais (eng) Mots-clés : Animals  Attention Deficit Disorder with Hyperactivity/metabolism/pathology  Autism Spectrum Disorder/metabolism/pathology  Behavior, Animal  Brain/metabolism/pathology  Disease Models, Animal  Female  Genotype  Glycoproteins/genetics/metabolism  Interneurons/metabolism  Male  Memory, Short-Term  Mice  Mice, Inbred C57BL  Mice, Knockout  Motor Activity  Nerve Tissue Proteins/deficiency/genetics/metabolism  Parvalbumins/genetics/metabolism  Phenotype  Real-Time Polymerase Chain Reaction  Vocalization, Animal  Autism spectrum disorder  Brinp1  Cortex  Hyperactivity  Interneuron  Knock-out  Neurodevelopment  Parvalbumin Index. décimale : PER Périodiques Résumé : BACKGROUND: BMP/RA-inducible neural-specific protein 1 (Brinp1) is highly conserved in vertebrates, and continuously expressed in the neocortex, hippocampus, olfactory bulb and cerebellum from mid-embryonic development through to adulthood. METHODS: Brinp1 knock-out (Brinp1(-/-)) mice were generated by Cre-recombinase-mediated removal of the third exon of Brinp1. Knock-out mice were characterised by behavioural phenotyping, immunohistochemistry and expression analysis of the developing and adult brain. RESULTS: Absence of Brinp1 during development results in a behavioural phenotype resembling autism spectrum disorder (ASD), in which knock-out mice show reduced sociability and changes in vocalisation capacity. In addition, Brinp1(-/-) mice exhibit hyper-locomotor activity, have impaired short-term memory, and exhibit poor reproductive success. Brinp1(-/-) mice show increased density of parvalbumin-expressing interneurons in the adult mouse brain. Brinp1(-/-) mice do not show signs of altered neural precursor proliferation or increased apoptosis during late embryonic brain development. The expression of the related neuronal migration genes Astn1 and Astn2 is increased in the brains of Brinp1(-/-) mice, suggesting that they may ameliorate the effects of Brinp1 loss. CONCLUSIONS: Brinp1 plays an important role in normal brain development and function by influencing neuronal distribution within the cortex. The increased cortical PV-positive interneuron density and altered behaviour of Brinp1(-/-) mice resemble features of a subset of human neurological disorders; namely autism spectrum disorder (ASD) and the hyperactivity aspect of attention deficit hyperactivity disorder (ADHD). En ligne : http://dx.doi.org/10.1186/s13229-016-0079-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 [article] Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density [texte imprimé] / Susan R. BERKOWICZ, Auteur ; Travis J. FEATHERBY, Auteur ; Zhengdong QU, Auteur ; Aminah GIOUSOH, Auteur ; Natalie A. BORG, Auteur ; Julian I. HENG, Auteur ; James C. WHISSTOCK, Auteur ; P.I. BIRD, Auteur . - 22p. Langues : Anglais (eng) in Molecular Autism > 7 (2016) . - 22p. Mots-clés : Animals  Attention Deficit Disorder with Hyperactivity/metabolism/pathology  Autism Spectrum Disorder/metabolism/pathology  Behavior, Animal  Brain/metabolism/pathology  Disease Models, Animal  Female  Genotype  Glycoproteins/genetics/metabolism  Interneurons/metabolism  Male  Memory, Short-Term  Mice  Mice, Inbred C57BL  Mice, Knockout  Motor Activity  Nerve Tissue Proteins/deficiency/genetics/metabolism  Parvalbumins/genetics/metabolism  Phenotype  Real-Time Polymerase Chain Reaction  Vocalization, Animal  Autism spectrum disorder  Brinp1  Cortex  Hyperactivity  Interneuron  Knock-out  Neurodevelopment  Parvalbumin Index. décimale : PER Périodiques Résumé : BACKGROUND: BMP/RA-inducible neural-specific protein 1 (Brinp1) is highly conserved in vertebrates, and continuously expressed in the neocortex, hippocampus, olfactory bulb and cerebellum from mid-embryonic development through to adulthood. METHODS: Brinp1 knock-out (Brinp1(-/-)) mice were generated by Cre-recombinase-mediated removal of the third exon of Brinp1. Knock-out mice were characterised by behavioural phenotyping, immunohistochemistry and expression analysis of the developing and adult brain. RESULTS: Absence of Brinp1 during development results in a behavioural phenotype resembling autism spectrum disorder (ASD), in which knock-out mice show reduced sociability and changes in vocalisation capacity. In addition, Brinp1(-/-) mice exhibit hyper-locomotor activity, have impaired short-term memory, and exhibit poor reproductive success. Brinp1(-/-) mice show increased density of parvalbumin-expressing interneurons in the adult mouse brain. Brinp1(-/-) mice do not show signs of altered neural precursor proliferation or increased apoptosis during late embryonic brain development. The expression of the related neuronal migration genes Astn1 and Astn2 is increased in the brains of Brinp1(-/-) mice, suggesting that they may ameliorate the effects of Brinp1 loss. CONCLUSIONS: Brinp1 plays an important role in normal brain development and function by influencing neuronal distribution within the cortex. The increased cortical PV-positive interneuron density and altered behaviour of Brinp1(-/-) mice resemble features of a subset of human neurological disorders; namely autism spectrum disorder (ASD) and the hyperactivity aspect of attention deficit hyperactivity disorder (ADHD). En ligne : http://dx.doi.org/10.1186/s13229-016-0079-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328

Increased 2-arachidonoyl-sn-glycerol levels normalize cortical responses to sound and improve behaviors in Fmr1 KO mice / Patricia S. PIRBHOY in Journal of Neurodevelopmental Disorders, 13 (2021)  

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Learning impairments in Fmr1(-/-)mice on an audio-visual temporal pattern discrimination task / William MOL in Journal of Neurodevelopmental Disorders, 17 (2025)  

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Communication and social interaction in the cannabinoid-type 1 receptor null mouse: Implications for autism spectrum disorder / William FYKE in Autism Research, 14-9 (September 2021)  

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Deep phenotyping reveals movement phenotypes in mouse neurodevelopmental models / Ugne KLIBAITE in Molecular Autism, 13 (2022)  

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Deletion of Fmr1 in parvalbumin-expressing neurons results in dysregulated translation and selective behavioral deficits associated with fragile X syndrome / Magdalena KALINOWSKA in Molecular Autism, 13 (2022)  

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