40 recherche sur le mot-clé 'Mice'

Brinp1(-/-) mice exhibit autism-like behaviour, altered memory, hyperactivity and increased parvalbumin-positive cortical interneuron density / S. 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 et/ou numérique Auteurs : S. R. BERKOWICZ, Auteur ; T. J. FEATHERBY, Auteur ; Z. QU, Auteur ; A. GIOUSOH, Auteur ; N. A. BORG, Auteur ; J. I. HENG, Auteur ; J. 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 et/ou numérique] / S. R. BERKOWICZ, Auteur ; T. J. FEATHERBY, Auteur ; Z. QU, Auteur ; A. GIOUSOH, Auteur ; N. A. BORG, Auteur ; J. I. HENG, Auteur ; J. 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

Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging / J. ELLEGOOD in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 24p. Titre : Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging Type de document : Texte imprimé et/ou numérique Auteurs : J. ELLEGOOD, Auteur ; Y. YEE, Auteur ; T. M. KERR, Auteur ; C. L. MULLER, Auteur ; R. D. BLAKELY, Auteur ; R. M. HENKELMAN, Auteur ; J. VEENSTRA-VANDERWEELE, Auteur ; J. P. LERCH, Auteur Article en page(s) : 24p. Langues : Anglais (eng) Mots-clés : Animals  Brain/diagnostic imaging/metabolism  Female  Magnetic Resonance Imaging  Male  Mice  Mice, Inbred C57BL  Mutation  Neurons/metabolism  Serotonin/metabolism  Serotonin Plasma Membrane Transport Proteins/genetics/metabolism  5-ht  5htt  Brain  Dorsal raphe  Magnetic resonance imaging  Neurodevelopment  Serotonin  Slc6a4 Index. décimale : PER Périodiques Résumé : Background: The serotonin (5-HT) system has long been implicated in autism spectrum disorder (ASD) as indicated by elevated whole blood and platelet 5-HT, altered platelet and brain receptor and transporter binding, and genetic linkage and association findings. Based upon work in genetically modified mice, 5-HT is known to influence several aspects of brain development, but systematic neuroimaging studies have not previously been reported. In particular, the 5-HT transporter (serotonin transporter, SERT; 5-HTT) gene, Slc6a4, has been extensively studied. Methods: Using a 7-T MRI and deformation-based morphometry, we assessed neuroanatomical differences in an Slc6a4 knockout mouse on a C57BL/6 genetic background, along with an Slc6a4 Ala56 knockin mouse on two different genetic backgrounds (129S and C57BL/6). Results: Individually (same sex, same background, same genotype), the only differences found were in the female Slc6a4 knockout mouse; all the others had no significant differences. However, an analysis of variance across the whole study sample revealed a significant effect of Slc6a4 on the amygdala, thalamus, dorsal raphe nucleus, and lateral and frontal cortices. Conclusions: This work shows that an increase or decrease in SERT function has a significant effect on the neuroanatomy in 5-HT relevant regions, particularly the raphe nuclei. Notably, the Slc6a4 Ala56 knockin alone appears to have an insignificant, but suggestive, effect compared to the KO, which is consistent with Slc6a4 function. Despite the small number of 5-HT neurons and their localization to the brainstem, it is clear that 5-HT plays an important role in neuroanatomical organization. En ligne : https://dx.doi.org/10.1186/s13229-018-0210-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging [Texte imprimé et/ou numérique] / J. ELLEGOOD, Auteur ; Y. YEE, Auteur ; T. M. KERR, Auteur ; C. L. MULLER, Auteur ; R. D. BLAKELY, Auteur ; R. M. HENKELMAN, Auteur ; J. VEENSTRA-VANDERWEELE, Auteur ; J. P. LERCH, Auteur . - 24p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 24p. Mots-clés : Animals  Brain/diagnostic imaging/metabolism  Female  Magnetic Resonance Imaging  Male  Mice  Mice, Inbred C57BL  Mutation  Neurons/metabolism  Serotonin/metabolism  Serotonin Plasma Membrane Transport Proteins/genetics/metabolism  5-ht  5htt  Brain  Dorsal raphe  Magnetic resonance imaging  Neurodevelopment  Serotonin  Slc6a4 Index. décimale : PER Périodiques Résumé : Background: The serotonin (5-HT) system has long been implicated in autism spectrum disorder (ASD) as indicated by elevated whole blood and platelet 5-HT, altered platelet and brain receptor and transporter binding, and genetic linkage and association findings. Based upon work in genetically modified mice, 5-HT is known to influence several aspects of brain development, but systematic neuroimaging studies have not previously been reported. In particular, the 5-HT transporter (serotonin transporter, SERT; 5-HTT) gene, Slc6a4, has been extensively studied. Methods: Using a 7-T MRI and deformation-based morphometry, we assessed neuroanatomical differences in an Slc6a4 knockout mouse on a C57BL/6 genetic background, along with an Slc6a4 Ala56 knockin mouse on two different genetic backgrounds (129S and C57BL/6). Results: Individually (same sex, same background, same genotype), the only differences found were in the female Slc6a4 knockout mouse; all the others had no significant differences. However, an analysis of variance across the whole study sample revealed a significant effect of Slc6a4 on the amygdala, thalamus, dorsal raphe nucleus, and lateral and frontal cortices. Conclusions: This work shows that an increase or decrease in SERT function has a significant effect on the neuroanatomy in 5-HT relevant regions, particularly the raphe nuclei. Notably, the Slc6a4 Ala56 knockin alone appears to have an insignificant, but suggestive, effect compared to the KO, which is consistent with Slc6a4 function. Despite the small number of 5-HT neurons and their localization to the brainstem, it is clear that 5-HT plays an important role in neuroanatomical organization. En ligne : https://dx.doi.org/10.1186/s13229-018-0210-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

Behavioral decline in Shank3(?ex4-22) mice during early adulthood parallels cerebellar granule cell glutamatergic synaptic changes / James O BEAVERS ; Romana HYDE ; Roseline EWA ; Amber SCHWERTMAN ; Sarahi PORCAYO ; Ben D RICHARDSON in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 52 Titre : Behavioral decline in Shank3(?ex4-22) mice during early adulthood parallels cerebellar granule cell glutamatergic synaptic changes Type de document : Texte imprimé et/ou numérique Auteurs : James O BEAVERS, Auteur ; Romana HYDE, Auteur ; Roseline EWA, Auteur ; Amber SCHWERTMAN, Auteur ; Sarahi PORCAYO, Auteur ; Ben D RICHARDSON, Auteur Article en page(s) : 52 Langues : Anglais (eng) Mots-clés : Animals  *Nerve Tissue Proteins/metabolism/genetics  *Mice, Knockout  *Synapses/metabolism  Male  *Behavior, Animal  Mice  *Excitatory Postsynaptic Potentials  Female  *Cerebellum/metabolism  Microfilament Proteins/metabolism/genetics  Glutamic Acid/metabolism  Exons  Mice, Inbred C57BL  Neurons/metabolism  Ampar  Autism spectrum disorder  Cerebellum  Glutamate receptor  Granule cell  Mouse behavior  Phelan-McDermid syndrome  Shank3  accordance with protocols approved by the Institutional Animal Care and Use  Committee at Southern Illinois Universe - School of Medicine or the University of  Idaho. Consent for publication: Not applicable. Competing interests: The authors  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: SHANK3, a gene encoding a synaptic scaffolding protein, is implicated in autism spectrum disorder (ASD) and is disrupted in Phelan-McDermid syndrome (PMS). Despite evidence of regression or worsening of ASD-like symptoms in individuals with PMS, the underlying mechanisms remain unclear. Although Shank3 is highly expressed in the cerebellar cortical granule cells, its role in cerebellar function and contribution to behavioral deficits in ASD models are unknown. This study investigates behavioral changes and cerebellar synaptic alterations in Shank3(?ex4-22) mice at two developmental stages. METHODS: Shank3(?ex4-22) wildtype, heterozygous, and homozygous knockout mice lacking exons 4-22 (all functional isoforms) were subjected to a behavioral battery in both juvenile (5-7 weeks old) and adult (3-5 months old) mouse cohorts of both sexes. Immunostaining was used to show the expression of Shank3 in the cerebellar cortex. Spontaneous excitatory postsynaptic currents (sEPSCs) from cerebellar granule cells (CGCs) were recorded by whole-cell patch-clamp electrophysiology. RESULTS: Deletion of Shank3 caused deficits in motor function, heightened anxiety, and repetitive behaviors. These genotype-dependent behavioral alterations were more prominent in adult mice than in juveniles. Reduced social preference was only identified in adult Shank3(?ex4-22) knockout male mice, while self-grooming was uniquely elevated in males across both age groups. Heterozygous mice showed little to no changes in behavioral phenotypes in most behavioral tests. Immunofluorescence staining indicated the presence of Shank3 predominantly in the dendrite-containing rosette-like structures in CGCs, colocalizing with presynaptic markers of glutamatergic mossy fiber. Electrophysiological findings identified a parallel relationship between the age-related exacerbation of behavioral impairments and the enhancement of sEPSC amplitude in CGCs. LIMITATIONS: Other behavioral tests of muscle strength (grip strength test), memory (Barnes/water maze), and communication (ultrasonic vocalization), were not performed. Further study is necessary to elucidate how Shank3 modulates synaptic function at the mossy fiber-granule cell synapse in the cerebellum and whether these changes shape the behavioral phenotype. CONCLUSIONS: Our findings reveal an age-related exacerbation of behavioral impairments in Shank3(?ex4-22) mutant mice. These results suggest that Shank3 may alter the function of glutamatergic receptors at the mossy fiber-cerebellar granule cell synapse as a potential mechanism causing cerebellar disruption in ASD. En ligne : https://dx.doi.org/10.1186/s13229-024-00628-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555 [article] Behavioral decline in Shank3(?ex4-22) mice during early adulthood parallels cerebellar granule cell glutamatergic synaptic changes [Texte imprimé et/ou numérique] / James O BEAVERS, Auteur ; Romana HYDE, Auteur ; Roseline EWA, Auteur ; Amber SCHWERTMAN, Auteur ; Sarahi PORCAYO, Auteur ; Ben D RICHARDSON, Auteur . - 52. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 52 Mots-clés : Animals  *Nerve Tissue Proteins/metabolism/genetics  *Mice, Knockout  *Synapses/metabolism  Male  *Behavior, Animal  Mice  *Excitatory Postsynaptic Potentials  Female  *Cerebellum/metabolism  Microfilament Proteins/metabolism/genetics  Glutamic Acid/metabolism  Exons  Mice, Inbred C57BL  Neurons/metabolism  Ampar  Autism spectrum disorder  Cerebellum  Glutamate receptor  Granule cell  Mouse behavior  Phelan-McDermid syndrome  Shank3  accordance with protocols approved by the Institutional Animal Care and Use  Committee at Southern Illinois Universe - School of Medicine or the University of  Idaho. Consent for publication: Not applicable. Competing interests: The authors  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: SHANK3, a gene encoding a synaptic scaffolding protein, is implicated in autism spectrum disorder (ASD) and is disrupted in Phelan-McDermid syndrome (PMS). Despite evidence of regression or worsening of ASD-like symptoms in individuals with PMS, the underlying mechanisms remain unclear. Although Shank3 is highly expressed in the cerebellar cortical granule cells, its role in cerebellar function and contribution to behavioral deficits in ASD models are unknown. This study investigates behavioral changes and cerebellar synaptic alterations in Shank3(?ex4-22) mice at two developmental stages. METHODS: Shank3(?ex4-22) wildtype, heterozygous, and homozygous knockout mice lacking exons 4-22 (all functional isoforms) were subjected to a behavioral battery in both juvenile (5-7 weeks old) and adult (3-5 months old) mouse cohorts of both sexes. Immunostaining was used to show the expression of Shank3 in the cerebellar cortex. Spontaneous excitatory postsynaptic currents (sEPSCs) from cerebellar granule cells (CGCs) were recorded by whole-cell patch-clamp electrophysiology. RESULTS: Deletion of Shank3 caused deficits in motor function, heightened anxiety, and repetitive behaviors. These genotype-dependent behavioral alterations were more prominent in adult mice than in juveniles. Reduced social preference was only identified in adult Shank3(?ex4-22) knockout male mice, while self-grooming was uniquely elevated in males across both age groups. Heterozygous mice showed little to no changes in behavioral phenotypes in most behavioral tests. Immunofluorescence staining indicated the presence of Shank3 predominantly in the dendrite-containing rosette-like structures in CGCs, colocalizing with presynaptic markers of glutamatergic mossy fiber. Electrophysiological findings identified a parallel relationship between the age-related exacerbation of behavioral impairments and the enhancement of sEPSC amplitude in CGCs. LIMITATIONS: Other behavioral tests of muscle strength (grip strength test), memory (Barnes/water maze), and communication (ultrasonic vocalization), were not performed. Further study is necessary to elucidate how Shank3 modulates synaptic function at the mossy fiber-granule cell synapse in the cerebellum and whether these changes shape the behavioral phenotype. CONCLUSIONS: Our findings reveal an age-related exacerbation of behavioral impairments in Shank3(?ex4-22) mutant mice. These results suggest that Shank3 may alter the function of glutamatergic receptors at the mossy fiber-cerebellar granule cell synapse as a potential mechanism causing cerebellar disruption in ASD. En ligne : https://dx.doi.org/10.1186/s13229-024-00628-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=555

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 et/ou numérique 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 et/ou numérique] / 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

Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice / R. T. MOLENHUIS in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 63 p. Titre : Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice Type de document : Texte imprimé et/ou numérique Auteurs : R. T. MOLENHUIS, Auteur ; Hilgo BRUINING, Auteur ; M. J. V. BRANDT, Auteur ; P. E. VAN SOLDT, Auteur ; H. J. ABU-TOAMIH ATAMNI, Auteur ; J. P. H. BURBACH, Auteur ; F. A. IRAQI, Auteur ; R. F. MOTT, Auteur ; M. J. H. KAS, Auteur Article en page(s) : 63 p. Langues : Anglais (eng) Mots-clés : Animals  Autism Spectrum Disorder/*genetics  Genetics, Behavioral/*methods/standards  Genome-Wide Association Study/*methods/standards  Male  Mice  Mice, Inbred C57BL  Multifactorial Inheritance  Quantitative Trait Loci  Reference Standards  *Animal models  *Autism  *Behavioral neuroscience  *Genetic reference population  *Histamine 3 receptor  *Neurodevelopmental disorders  *Quantitative genetics  *Repetitive behavior  Care and Use Committee of Tel Aviv University.Not applicable.The authors declare  that they have no competing interests.Springer Nature remains neutral with regard  to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Animal models for neurodevelopmental disorders (NDD) generally rely on a single genetic mutation on a fixed genetic background. Recent human genetic studies however indicate that a clinical diagnosis with ASDAutism Spectrum Disorder (ASD) is almost always associated with multiple genetic fore- and background changes. The translational value of animal model studies would be greatly enhanced if genetic insults could be studied in a more quantitative framework across genetic backgrounds. Methods: We used the Collaborative Cross (CC), a novel mouse genetic reference population, to investigate the quantitative genetic architecture of mouse behavioral phenotypes commonly used in animal models for NDD. Results: Classical tests of social recognition and grooming phenotypes appeared insufficient for quantitative studies due to genetic dilution and limited heritability. In contrast, digging, locomotor activity, and stereotyped exploratory patterns were characterized by continuous distribution across our CC sample and also mapped to quantitative trait loci containing genes associated with corresponding phenotypes in human populations. Conclusions: These findings show that the CC can move animal model studies beyond comparative single gene-single background designs, and point out which type of behavioral phenotypes are most suitable to quantify the effect of developmental etiologies across multiple genetic backgrounds. En ligne : https://dx.doi.org/10.1186/s13229-018-0252-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389 [article] Modeling the quantitative nature of neurodevelopmental disorders using Collaborative Cross mice [Texte imprimé et/ou numérique] / R. T. MOLENHUIS, Auteur ; Hilgo BRUINING, Auteur ; M. J. V. BRANDT, Auteur ; P. E. VAN SOLDT, Auteur ; H. J. ABU-TOAMIH ATAMNI, Auteur ; J. P. H. BURBACH, Auteur ; F. A. IRAQI, Auteur ; R. F. MOTT, Auteur ; M. J. H. KAS, Auteur . - 63 p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 63 p. Mots-clés : Animals  Autism Spectrum Disorder/*genetics  Genetics, Behavioral/*methods/standards  Genome-Wide Association Study/*methods/standards  Male  Mice  Mice, Inbred C57BL  Multifactorial Inheritance  Quantitative Trait Loci  Reference Standards  *Animal models  *Autism  *Behavioral neuroscience  *Genetic reference population  *Histamine 3 receptor  *Neurodevelopmental disorders  *Quantitative genetics  *Repetitive behavior  Care and Use Committee of Tel Aviv University.Not applicable.The authors declare  that they have no competing interests.Springer Nature remains neutral with regard  to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Animal models for neurodevelopmental disorders (NDD) generally rely on a single genetic mutation on a fixed genetic background. Recent human genetic studies however indicate that a clinical diagnosis with ASDAutism Spectrum Disorder (ASD) is almost always associated with multiple genetic fore- and background changes. The translational value of animal model studies would be greatly enhanced if genetic insults could be studied in a more quantitative framework across genetic backgrounds. Methods: We used the Collaborative Cross (CC), a novel mouse genetic reference population, to investigate the quantitative genetic architecture of mouse behavioral phenotypes commonly used in animal models for NDD. Results: Classical tests of social recognition and grooming phenotypes appeared insufficient for quantitative studies due to genetic dilution and limited heritability. In contrast, digging, locomotor activity, and stereotyped exploratory patterns were characterized by continuous distribution across our CC sample and also mapped to quantitative trait loci containing genes associated with corresponding phenotypes in human populations. Conclusions: These findings show that the CC can move animal model studies beyond comparative single gene-single background designs, and point out which type of behavioral phenotypes are most suitable to quantify the effect of developmental etiologies across multiple genetic backgrounds. En ligne : https://dx.doi.org/10.1186/s13229-018-0252-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=389

Pharmacological inhibition of the primary endocannabinoid producing enzyme, DGL-?, induces autism spectrum disorder-like and co-morbid phenotypes in adult C57BL/J mice / W. FYKE in Autism Research, 14-7 (July 2021)  

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Postnatal downregulation of Fmr1 in microglia promotes microglial reactivity and causes behavioural alterations in female mice / David HO-TIENG ; Kevin C LISTER ; Weihua CAI ; Calvin WONG ; Nicole BROWN ; Jonathan FAN ; Volodya HOVHANNISYAN ; Sonali UTTAM ; Masha PRAGER-KHOUTORSKY ; Nahum SONENBERG ; Christos G GKOGKAS ; Arkady KHOUTORSKY in Molecular Autism, 16 (2025)  

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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)  

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Autistic behavior is a common outcome of biallelic disruption of PDZD8 in humans and mice / Stijn VAN DE SOMPELE ; Clemence LIGNEUL ; Camille CHATELAIN ; Christophe BARREA ; Jason P LERCH ; Beatrice M FILIPPI ; Serpil ALKAN ; Elfride DE BAERE ; Jamie JOHNSTON ; Steven J CLAPCOTE in Molecular Autism, 16 (2025)  

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

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