A 15q11–q13 Duplication Mouse Model of Autism Spectrum Disorders / Toru TAKUMI

Public ISBD in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM Titre : A 15q11–q13 Duplication Mouse Model of Autism Spectrum Disorders Type de document : texte imprimé Auteurs : Toru TAKUMI, Auteur ; Keita FUKUMOTO, Auteur ; Jun NOMURA, Auteur Année de publication : 2013 Importance : p.401-408 Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Autism spectrum disorders (ASD) are developmental brain disorders manifested by abnormal social behavior. Recent human genetic studies have revealed various copy number variations in ASD. Duplication of human chromosome 15q11–q13 is known to be most frequently associated with cytogenetic abnormality in ASD. Human chromosome 15q11–q13, also known to include imprinted genes, is well conserved to mouse chromosome 7. By a chromosome-engineering technique, we developed a mouse model for 15q11–q13 duplication. Paternally derived duplication (patDp/+) mice show abnormal behavior including abnormal social interaction, alteration in the developmental course of ultrasonic vocalizations, and resistance to change in reversal learning. Reduced serotonin (5-HT) is observed in the brain of patDp/+ mice during development, suggesting that this abnormal 5-HT level may affect social behavior. A 15q11–q13 duplication model mouse will facilitate future studies in genetics of developmental brain disorders and serve as an invaluable tool for therapeutic development. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=189 in The Neuroscience of Autism Spectrum Disorders / Joseph D. BUXBAUM A 15q11–q13 Duplication Mouse Model of Autism Spectrum Disorders [texte imprimé] / Toru TAKUMI, Auteur ; Keita FUKUMOTO, Auteur ; Jun NOMURA, Auteur . - 2013 . - p.401-408. Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Autism spectrum disorders (ASD) are developmental brain disorders manifested by abnormal social behavior. Recent human genetic studies have revealed various copy number variations in ASD. Duplication of human chromosome 15q11–q13 is known to be most frequently associated with cytogenetic abnormality in ASD. Human chromosome 15q11–q13, also known to include imprinted genes, is well conserved to mouse chromosome 7. By a chromosome-engineering technique, we developed a mouse model for 15q11–q13 duplication. Paternally derived duplication (patDp/+) mice show abnormal behavior including abnormal social interaction, alteration in the developmental course of ultrasonic vocalizations, and resistance to change in reversal learning. Reduced serotonin (5-HT) is observed in the brain of patDp/+ mice during development, suggesting that this abnormal 5-HT level may affect social behavior. A 15q11–q13 duplication model mouse will facilitate future studies in genetics of developmental brain disorders and serve as an invaluable tool for therapeutic development. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=189

Exemplaires(0)

Disponibilité
aucun exemplaire

Germ-cell-specific transcriptome analysis illuminates the chromatin and ubiquitin pathway in autism spectrum disorders / Sawako FURUKAWA in Autism Research, 16-6 (June 2023)  

Public ISBD [article]  inAutism Research > 16-6 (June 2023) . - p.1101-1110 Titre : Germ-cell-specific transcriptome analysis illuminates the chromatin and ubiquitin pathway in autism spectrum disorders Type de document : texte imprimé Auteurs : Sawako FURUKAWA, Auteur ; Jun NOMURA, Auteur ; Hiroaki HANAFUSA, Auteur ; Hiroko MAEGAWA, Auteur ; Toru TAKUMI, Auteur Article en page(s) : p.1101-1110 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  bioinformatics  copy number variants  embryonic stem cells  germ cells  single-cell analysis Index. décimale : PER Périodiques Résumé : Abstract Accumulating epidemiological studies have suggested a positive association between advanced paternal age at conception and the increased risk of neurodevelopmental outcomes such as autism spectrum disorder (ASD) in their children. Recent biological studies using human sperm have identified increased de novo mutations in aged fathers, and hyper- or hypomethylation has been identified in the sperm from aged rodents. Dysregulation of DNA methylation in sperm may explain the transgenerational effects on the pathogenesis of ASD. However, compared to these epigenetic changes in the sperm of aged males, the effects of inherited predisposition from germ cells are largely unknown. Here, we use single-cell transcriptome data sets from 13 cell lines, including 12 ASD-associated CNVs models and control, that are performed neural differentiation from mouse embryonic stem cells. This study performed comprehensive bioinformatic analyses such as gene ontology (GO), network, pathway, and upstream regulator analyses. Through these analyses, we identify several susceptible pathways, such as chromatin and ubiquitin, in addition to translational and oxidative phosphorylation. Our results suggest that dysregulation of epigenetic chromosome remodeling and ubiquitin-proteasome pathway in the germ cell is a possible modulator for subsequent differentiated cells, sperm, and egg, as a risk factor for the neurodevelopmental disorder. En ligne : https://doi.org/10.1002/aur.2939 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=507 [article] Germ-cell-specific transcriptome analysis illuminates the chromatin and ubiquitin pathway in autism spectrum disorders [texte imprimé] / Sawako FURUKAWA, Auteur ; Jun NOMURA, Auteur ; Hiroaki HANAFUSA, Auteur ; Hiroko MAEGAWA, Auteur ; Toru TAKUMI, Auteur . - p.1101-1110. Langues : Anglais (eng) in Autism Research > 16-6 (June 2023) . - p.1101-1110 Mots-clés : autism spectrum disorder  bioinformatics  copy number variants  embryonic stem cells  germ cells  single-cell analysis Index. décimale : PER Périodiques Résumé : Abstract Accumulating epidemiological studies have suggested a positive association between advanced paternal age at conception and the increased risk of neurodevelopmental outcomes such as autism spectrum disorder (ASD) in their children. Recent biological studies using human sperm have identified increased de novo mutations in aged fathers, and hyper- or hypomethylation has been identified in the sperm from aged rodents. Dysregulation of DNA methylation in sperm may explain the transgenerational effects on the pathogenesis of ASD. However, compared to these epigenetic changes in the sperm of aged males, the effects of inherited predisposition from germ cells are largely unknown. Here, we use single-cell transcriptome data sets from 13 cell lines, including 12 ASD-associated CNVs models and control, that are performed neural differentiation from mouse embryonic stem cells. This study performed comprehensive bioinformatic analyses such as gene ontology (GO), network, pathway, and upstream regulator analyses. Through these analyses, we identify several susceptible pathways, such as chromatin and ubiquitin, in addition to translational and oxidative phosphorylation. Our results suggest that dysregulation of epigenetic chromosome remodeling and ubiquitin-proteasome pathway in the germ cell is a possible modulator for subsequent differentiated cells, sperm, and egg, as a risk factor for the neurodevelopmental disorder. En ligne : https://doi.org/10.1002/aur.2939 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=507

Neuroanatomical Phenotypes Are Consistent With Autism-Like Behavioral Phenotypes in the 15q11-13 Duplication Mouse Model / Jacob ELLEGOOD in Autism Research, 8-5 (October 2015)  

Public ISBD [article]  inAutism Research > 8-5 (October 2015) . - p.545-555 Titre : Neuroanatomical Phenotypes Are Consistent With Autism-Like Behavioral Phenotypes in the 15q11-13 Duplication Mouse Model Type de document : texte imprimé Auteurs : Jacob ELLEGOOD, Auteur ; Nobuhiro NAKAI, Auteur ; Jin NAKATANI, Auteur ; R. Mark HENKELMAN, Auteur ; Toru TAKUMI, Auteur ; Jason P. LERCH, Auteur Article en page(s) : p.545-555 Langues : Anglais (eng) Mots-clés : animal models  structural MRI  neuroanatomy  copy number variation  molecular genetics  15q11-13 duplication Index. décimale : PER Périodiques Résumé : Paternally and maternally inherited deletions and duplications of human chromosome 15q11-13 are relatively common in the human population. Furthermore, duplications in the 15q region are often associated with autism. Both maternal and paternal interstitial 15q11-13 duplication mouse models have been previously created, where several behavioral differences were found in the paternal duplication (patDp/+) mouse but not in the maternal duplication (matDp/+). These included decreased sociability, behavioral inflexibility, abnormal ultrasonic vocalizations, decreased spontaneous activity, and increased anxiety. Similarly, in the current study, we found several anatomical differences in the patDp/+ mice that were not seen in the matDp/+ mice. Regional differences that are evident only in the paternal duplication are a smaller dentate gyrus and smaller medial striatum. These differences may be responsible for the behavioral inflexibility. Furthermore, a smaller dorsal raphe nucleus could be responsible for the reported serotonin defects. This study highlights consistency that can be found between behavioral and anatomical phenotyping. Autism Res 2015, 8: 545–555. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1469 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=270 [article] Neuroanatomical Phenotypes Are Consistent With Autism-Like Behavioral Phenotypes in the 15q11-13 Duplication Mouse Model [texte imprimé] / Jacob ELLEGOOD, Auteur ; Nobuhiro NAKAI, Auteur ; Jin NAKATANI, Auteur ; R. Mark HENKELMAN, Auteur ; Toru TAKUMI, Auteur ; Jason P. LERCH, Auteur . - p.545-555. Langues : Anglais (eng) in Autism Research > 8-5 (October 2015) . - p.545-555 Mots-clés : animal models  structural MRI  neuroanatomy  copy number variation  molecular genetics  15q11-13 duplication Index. décimale : PER Périodiques Résumé : Paternally and maternally inherited deletions and duplications of human chromosome 15q11-13 are relatively common in the human population. Furthermore, duplications in the 15q region are often associated with autism. Both maternal and paternal interstitial 15q11-13 duplication mouse models have been previously created, where several behavioral differences were found in the paternal duplication (patDp/+) mouse but not in the maternal duplication (matDp/+). These included decreased sociability, behavioral inflexibility, abnormal ultrasonic vocalizations, decreased spontaneous activity, and increased anxiety. Similarly, in the current study, we found several anatomical differences in the patDp/+ mice that were not seen in the matDp/+ mice. Regional differences that are evident only in the paternal duplication are a smaller dentate gyrus and smaller medial striatum. These differences may be responsible for the behavioral inflexibility. Furthermore, a smaller dorsal raphe nucleus could be responsible for the reported serotonin defects. This study highlights consistency that can be found between behavioral and anatomical phenotyping. Autism Res 2015, 8: 545–555. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1469 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=270

Serotonin Disturbance in Mouse Models of Autism Spectrum Disorders / Kota TAMADA

Public ISBD in Organism models of autism spectrum disorders / Pierre L. ROUBERTOUX Titre : Serotonin Disturbance in Mouse Models of Autism Spectrum Disorders Type de document : texte imprimé Auteurs : Kota TAMADA, Auteur ; Toru TAKUMI, Auteur Année de publication : 2015 Importance : p.239-262 Langues : Anglais (eng) Mots-clés : 15q11–13 duplication  5-Hydroxytryptamine  Hyperserotonemia  VNTR  Tryptophan depletion  BALB/c mice  BTBR mice  Social interactions  Ultrasonic vocalizations  Inflexible behavior  Repetitive behavior  Self-grooming  Reversal learning  Thigmotaxis Index. décimale : AUT-B AUT-B - L'Autisme - Ouvrages généraux et scientifiques Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=265 in Organism models of autism spectrum disorders / Pierre L. ROUBERTOUX Serotonin Disturbance in Mouse Models of Autism Spectrum Disorders [texte imprimé] / Kota TAMADA, Auteur ; Toru TAKUMI, Auteur . - 2015 . - p.239-262. Langues : Anglais (eng) Mots-clés : 15q11–13 duplication  5-Hydroxytryptamine  Hyperserotonemia  VNTR  Tryptophan depletion  BALB/c mice  BTBR mice  Social interactions  Ultrasonic vocalizations  Inflexible behavior  Repetitive behavior  Self-grooming  Reversal learning  Thigmotaxis Index. décimale : AUT-B AUT-B - L'Autisme - Ouvrages généraux et scientifiques Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=265

Exemplaires(0)

Disponibilité
aucun exemplaire

Single-Cell Transcriptome Meta-Analysis Reveals Epigenomic and Chromatin Dysregulation in Developing Neurons Derived From Human ESCs With 1q21.1 CNVs / Kosuke TORIGATA in Autism Research, 19-1 (January 2026)  

Public ISBD [article]  inAutism Research > 19-1 (January 2026) . - p.e70156 Titre : Single-Cell Transcriptome Meta-Analysis Reveals Epigenomic and Chromatin Dysregulation in Developing Neurons Derived From Human ESCs With 1q21.1 CNVs Type de document : texte imprimé Auteurs : Kosuke TORIGATA, Auteur ; Jun NOMURA, Auteur ; Toru TAKUMI, Auteur Article en page(s) : p.e70156 Langues : Anglais (eng) Mots-clés : chromatin  copy number variation  epigenome  human ES cell  single-cell transcriptome Index. décimale : PER Périodiques Résumé : ABSTRACT Recent efforts to construct disease-specific multimodal omics databases at single-cell resolution, along with advances in reconstructive technologies such as brain organoids, have opened up opportunities to elucidate the molecular basis of complex human neuropsychiatric diseases. In this study, we performed a meta-analysis to characterize disease-associated regulatory modules by performing single-cell transcriptome analysis of developing neurons from reciprocal human ESC models of CNV in the distal 1q21.1 region. As a result, we observed significant directional enrichment of a series of genes in neuronal cells associated with autism spectrum disorder (ASD), bipolar disorder, and schizophrenia. Correlation analyses revealed that the disease-associated signature primarily targeted epigenetic regulatory mechanisms. We also identified Bromodomain PHD Finger Transcription Factor (BPTF), a key component of the NURF chromatin remodeling complex, as a potential target responsible for transcriptome changes related to human neuropsychiatric diseases, including ASD. We provide a practical and straightforward analytical workflow for utilizing both public data and in-house single-cell omics data from disease models. En ligne : https://doi.org/10.1002/aur.70156 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=578 [article] Single-Cell Transcriptome Meta-Analysis Reveals Epigenomic and Chromatin Dysregulation in Developing Neurons Derived From Human ESCs With 1q21.1 CNVs [texte imprimé] / Kosuke TORIGATA, Auteur ; Jun NOMURA, Auteur ; Toru TAKUMI, Auteur . - p.e70156. Langues : Anglais (eng) in Autism Research > 19-1 (January 2026) . - p.e70156 Mots-clés : chromatin  copy number variation  epigenome  human ES cell  single-cell transcriptome Index. décimale : PER Périodiques Résumé : ABSTRACT Recent efforts to construct disease-specific multimodal omics databases at single-cell resolution, along with advances in reconstructive technologies such as brain organoids, have opened up opportunities to elucidate the molecular basis of complex human neuropsychiatric diseases. In this study, we performed a meta-analysis to characterize disease-associated regulatory modules by performing single-cell transcriptome analysis of developing neurons from reciprocal human ESC models of CNV in the distal 1q21.1 region. As a result, we observed significant directional enrichment of a series of genes in neuronal cells associated with autism spectrum disorder (ASD), bipolar disorder, and schizophrenia. Correlation analyses revealed that the disease-associated signature primarily targeted epigenetic regulatory mechanisms. We also identified Bromodomain PHD Finger Transcription Factor (BPTF), a key component of the NURF chromatin remodeling complex, as a potential target responsible for transcriptome changes related to human neuropsychiatric diseases, including ASD. We provide a practical and straightforward analytical workflow for utilizing both public data and in-house single-cell omics data from disease models. En ligne : https://doi.org/10.1002/aur.70156 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=578

Sleep EEG signatures in mouse models of 15q11.2-13.1 duplication (Dup15q) syndrome / Vidya SARAVANAPANDIAN in Journal of Neurodevelopmental Disorders, 16 (2024)  

Permalink

The neurobiology of mouse models syntenic to human chromosome 15q / Toru TAKUMI in Journal of Neurodevelopmental Disorders, 3-3 (September 2011)  

Permalink

---

1 (1 - 7 / 7) Par page : 25 50 100 200