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A DLG2 deficiency in mice leads to reduced sociability and increased repetitive behavior accompanied by aberrant synaptic transmission in the dorsal striatum / Taesun YOO in Molecular Autism, 11 (2020)
[article]
Titre : A DLG2 deficiency in mice leads to reduced sociability and increased repetitive behavior accompanied by aberrant synaptic transmission in the dorsal striatum Type de document : Texte imprimé et/ou numérique Auteurs : Taesun YOO, Auteur ; Sun-Gyun KIM, Auteur ; Soo Hyun YANG, Auteur ; Hyun KIM, Auteur ; Eunjoon KIM, Auteur ; Soo Young KIM, Auteur Article en page(s) : 19 p. Langues : Anglais (eng) Mots-clés : Autism Locomotion psd-93 Self-grooming Social interaction Spiny projection Neurons Striatum Index. décimale : PER Périodiques Résumé : BACKGROUND: DLG2, also known as postsynaptic density protein-93 (PSD-93) or chapsyn-110, is an excitatory postsynaptic scaffolding protein that interacts with synaptic surface receptors and signaling molecules. A recent study has demonstrated that mutations in the DLG2 promoter region are significantly associated with autism spectrum disorder (ASD). Although DLG2 is well known as a schizophrenia-susceptibility gene, the mechanisms that link DLG2 gene disruption with ASD-like behaviors remain unclear. METHODS: Mice lacking exon 14 of the Dlg2 gene (Dlg2(-/-) mice) were used to investigate whether Dlg2 deletion leads to ASD-like behavioral abnormalities. To this end, we performed a battery of behavioral tests assessing locomotion, anxiety, sociability, and repetitive behaviors. In situ hybridization was performed to determine expression levels of Dlg2 mRNA in different mouse brain regions during embryonic and postnatal brain development. We also measured excitatory and inhibitory synaptic currents to determine the impacts of Dlg2 deletion on synaptic transmission in the dorsolateral striatum. RESULTS: Dlg2(-/-) mice showed hypoactivity in a novel environment. They also exhibited decreased social approach, but normal social novelty recognition, compared with wild-type animals. In addition, Dlg2(-/-) mice displayed strong self-grooming, both in home cages and novel environments. Dlg2 mRNA levels in the striatum were heightened until postnatal day 7 in mice, implying potential roles of DLG2 in the development of striatal connectivity. In addition, the frequency of excitatory, but not inhibitory, spontaneous postsynaptic currents in the Dlg2(-/-) dorsolateral striatum was significantly reduced. CONCLUSION: These results suggest that homozygous Dlg2 deletion in mice leads to ASD-like behavioral phenotypes, including social deficits and increased repetitive behaviors, as well as reductions in excitatory synaptic input onto dorsolateral spiny projection neurons, implying that the dorsal striatum is one of the brain regions vulnerable to the developmental dysregulation of DLG2. En ligne : http://dx.doi.org/10.1186/s13229-020-00324-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427
in Molecular Autism > 11 (2020) . - 19 p.[article] A DLG2 deficiency in mice leads to reduced sociability and increased repetitive behavior accompanied by aberrant synaptic transmission in the dorsal striatum [Texte imprimé et/ou numérique] / Taesun YOO, Auteur ; Sun-Gyun KIM, Auteur ; Soo Hyun YANG, Auteur ; Hyun KIM, Auteur ; Eunjoon KIM, Auteur ; Soo Young KIM, Auteur . - 19 p.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020) . - 19 p.
Mots-clés : Autism Locomotion psd-93 Self-grooming Social interaction Spiny projection Neurons Striatum Index. décimale : PER Périodiques Résumé : BACKGROUND: DLG2, also known as postsynaptic density protein-93 (PSD-93) or chapsyn-110, is an excitatory postsynaptic scaffolding protein that interacts with synaptic surface receptors and signaling molecules. A recent study has demonstrated that mutations in the DLG2 promoter region are significantly associated with autism spectrum disorder (ASD). Although DLG2 is well known as a schizophrenia-susceptibility gene, the mechanisms that link DLG2 gene disruption with ASD-like behaviors remain unclear. METHODS: Mice lacking exon 14 of the Dlg2 gene (Dlg2(-/-) mice) were used to investigate whether Dlg2 deletion leads to ASD-like behavioral abnormalities. To this end, we performed a battery of behavioral tests assessing locomotion, anxiety, sociability, and repetitive behaviors. In situ hybridization was performed to determine expression levels of Dlg2 mRNA in different mouse brain regions during embryonic and postnatal brain development. We also measured excitatory and inhibitory synaptic currents to determine the impacts of Dlg2 deletion on synaptic transmission in the dorsolateral striatum. RESULTS: Dlg2(-/-) mice showed hypoactivity in a novel environment. They also exhibited decreased social approach, but normal social novelty recognition, compared with wild-type animals. In addition, Dlg2(-/-) mice displayed strong self-grooming, both in home cages and novel environments. Dlg2 mRNA levels in the striatum were heightened until postnatal day 7 in mice, implying potential roles of DLG2 in the development of striatal connectivity. In addition, the frequency of excitatory, but not inhibitory, spontaneous postsynaptic currents in the Dlg2(-/-) dorsolateral striatum was significantly reduced. CONCLUSION: These results suggest that homozygous Dlg2 deletion in mice leads to ASD-like behavioral phenotypes, including social deficits and increased repetitive behaviors, as well as reductions in excitatory synaptic input onto dorsolateral spiny projection neurons, implying that the dorsal striatum is one of the brain regions vulnerable to the developmental dysregulation of DLG2. En ligne : http://dx.doi.org/10.1186/s13229-020-00324-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 Evaluation of Motor Skills in Children with Rubinstein-Taybi Syndrome / J. R. CAZALETS in Journal of Autism and Developmental Disorders, 47-11 (November 2017)
[article]
Titre : Evaluation of Motor Skills in Children with Rubinstein-Taybi Syndrome Type de document : Texte imprimé et/ou numérique Auteurs : J. R. CAZALETS, Auteur ; E. BESTAVEN, Auteur ; E. DOAT, Auteur ; M. P. BAUDIER, Auteur ; C. GALLOT, Auteur ; Anouck AMESTOY, Auteur ; Manuel P. BOUVARD, Auteur ; E. GUILLAUD, Auteur ; I. GUILLAIN, Auteur ; E. GRECH, Auteur ; J. VAN-GILS, Auteur ; P. FERGELOT, Auteur ; S. FRAISSE, Auteur ; E. TAUPIAC, Auteur ; Benoit ARVEILER, Auteur ; D. LACOMBE, Auteur Article en page(s) : p.3321-3332 Langues : Anglais (eng) Mots-clés : Gait Intellectual disability Locomotion Posture Rubinstein-Taybi syndrome Index. décimale : PER Périodiques Résumé : Rubinstein-Taybi syndrome (RTS) is a rare genetic disease that associates intellectual disability with somatic characteristics. We have conducted a study of the overall motor abilities of RTS participants. Static postural performance as well as gait parameters were somewhat decreased, although not significantly compared to typically developing (TD) participants. In contrast, the motor skills requiring a high level of visuomotor coordination were considerably degraded in RTS participants compared to TD participants. We also found that cognitive status was significantly correlated with performance for tasks requiring a higher level of visuomotor coordination in RTS but not TD participants. Our study demonstrates a reduction in the motor performance of RTS participants and a link between the level of intellectual disability and motor capacities. En ligne : http://dx.doi.org/10.1007/s10803-017-3259-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=324
in Journal of Autism and Developmental Disorders > 47-11 (November 2017) . - p.3321-3332[article] Evaluation of Motor Skills in Children with Rubinstein-Taybi Syndrome [Texte imprimé et/ou numérique] / J. R. CAZALETS, Auteur ; E. BESTAVEN, Auteur ; E. DOAT, Auteur ; M. P. BAUDIER, Auteur ; C. GALLOT, Auteur ; Anouck AMESTOY, Auteur ; Manuel P. BOUVARD, Auteur ; E. GUILLAUD, Auteur ; I. GUILLAIN, Auteur ; E. GRECH, Auteur ; J. VAN-GILS, Auteur ; P. FERGELOT, Auteur ; S. FRAISSE, Auteur ; E. TAUPIAC, Auteur ; Benoit ARVEILER, Auteur ; D. LACOMBE, Auteur . - p.3321-3332.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 47-11 (November 2017) . - p.3321-3332
Mots-clés : Gait Intellectual disability Locomotion Posture Rubinstein-Taybi syndrome Index. décimale : PER Périodiques Résumé : Rubinstein-Taybi syndrome (RTS) is a rare genetic disease that associates intellectual disability with somatic characteristics. We have conducted a study of the overall motor abilities of RTS participants. Static postural performance as well as gait parameters were somewhat decreased, although not significantly compared to typically developing (TD) participants. In contrast, the motor skills requiring a high level of visuomotor coordination were considerably degraded in RTS participants compared to TD participants. We also found that cognitive status was significantly correlated with performance for tasks requiring a higher level of visuomotor coordination in RTS but not TD participants. Our study demonstrates a reduction in the motor performance of RTS participants and a link between the level of intellectual disability and motor capacities. En ligne : http://dx.doi.org/10.1007/s10803-017-3259-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=324