Dépouillements

Commentary for Special Issue of Autism Research on Mouse Models in ASD: A Clinical Perspective / Nancy J. MINSHEW in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.1-4 Titre : Commentary for Special Issue of Autism Research on Mouse Models in ASD: A Clinical Perspective Type de document : Texte imprimé et/ou numérique Auteurs : Nancy J. MINSHEW, Auteur ; Kathryn MCFADDEN, Auteur Année de publication : 2011 Article en page(s) : p.1-4 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.185 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] Commentary for Special Issue of Autism Research on Mouse Models in ASD: A Clinical Perspective [Texte imprimé et/ou numérique] / Nancy J. MINSHEW, Auteur ; Kathryn MCFADDEN, Auteur . - 2011 . - p.1-4. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.1-4 Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.185 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118

Behavioral profiles of mouse models for autism spectrum disorders / Elodie EY in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.5-16 Titre : Behavioral profiles of mouse models for autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : Elodie EY, Auteur ; Claire S. LEBLOND, Auteur ; Thomas BOURGERON, Auteur Année de publication : 2011 Article en page(s) : p.5-16 Langues : Anglais (eng) Mots-clés : autism spectrum disorder  mouse model  synaptic pathway  mTOR/PI3K pathway  behavior Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are characterized by impairments in reciprocal social communication, and stereotyped verbal and nonverbal behaviors. In approximately 10–25% of the affected individuals, a genetic mutation associated with the condition can be identified. Recently, mutations altering synapse formation, cellular/synaptic growth rate and regulation of excitatory and inhibitory currents were identified in patients with intellectual disability, typical autism, Asperger syndrome or neurological syndromes associated with autistic traits. Following these genetic findings, mouse models carrying mutations similar to those identified in patients have been generated. These models offer the opportunity to investigate in vivo the physiological and behavioral consequences of the mutations. Here, we review the existing data on the phenotypes of mice carrying mutations in genes associated with ASD including neuroligin, neurexin and Shank mutant mice as well as the Fmr1, Mecp2, Ube3a, Nf1, Pten and Tsc1/Tsc2 mutant mice. The diversity and complexity of the phenotype of these mouse models reflect the broad range of phenotypes observed in patients with ASD. Remarkably, results from therapeutic approaches (e.g., modulation of gene expression, administration of pharmacological and nonpharmacological substances, enriched environment) are encouraging since some behavioral alterations could be reversed even when treatment was performed on adult mice. These ongoing studies should therefore increase our understanding of the biological alterations associated with ASD as well as the development of knowledge-based treatments. En ligne : http://dx.doi.org/10.1002/aur.175 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] Behavioral profiles of mouse models for autism spectrum disorders [Texte imprimé et/ou numérique] / Elodie EY, Auteur ; Claire S. LEBLOND, Auteur ; Thomas BOURGERON, Auteur . - 2011 . - p.5-16. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.5-16 Mots-clés : autism spectrum disorder  mouse model  synaptic pathway  mTOR/PI3K pathway  behavior Index. décimale : PER Périodiques Résumé : Autism spectrum disorders (ASD) are characterized by impairments in reciprocal social communication, and stereotyped verbal and nonverbal behaviors. In approximately 10–25% of the affected individuals, a genetic mutation associated with the condition can be identified. Recently, mutations altering synapse formation, cellular/synaptic growth rate and regulation of excitatory and inhibitory currents were identified in patients with intellectual disability, typical autism, Asperger syndrome or neurological syndromes associated with autistic traits. Following these genetic findings, mouse models carrying mutations similar to those identified in patients have been generated. These models offer the opportunity to investigate in vivo the physiological and behavioral consequences of the mutations. Here, we review the existing data on the phenotypes of mice carrying mutations in genes associated with ASD including neuroligin, neurexin and Shank mutant mice as well as the Fmr1, Mecp2, Ube3a, Nf1, Pten and Tsc1/Tsc2 mutant mice. The diversity and complexity of the phenotype of these mouse models reflect the broad range of phenotypes observed in patients with ASD. Remarkably, results from therapeutic approaches (e.g., modulation of gene expression, administration of pharmacological and nonpharmacological substances, enriched environment) are encouraging since some behavioral alterations could be reversed even when treatment was performed on adult mice. These ongoing studies should therefore increase our understanding of the biological alterations associated with ASD as well as the development of knowledge-based treatments. En ligne : http://dx.doi.org/10.1002/aur.175 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118

Social peers rescue autism-relevant sociability deficits in adolescent mice / Mu YANG in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.17-27 Titre : Social peers rescue autism-relevant sociability deficits in adolescent mice Type de document : Texte imprimé et/ou numérique Auteurs : Mu YANG, Auteur ; Kayla PERRY, Auteur ; Michael D. WEBER, Auteur ; Adam M. KATZ, Auteur ; Jacqueline N. CRAWLEY, Auteur Année de publication : 2011 Article en page(s) : p.17-27 Langues : Anglais (eng) Mots-clés : autism  BTBR inbred strain  mouse model  peer enrichment  social enrichment  behavioral intervention Index. décimale : PER Périodiques Résumé : Behavioral therapies are currently the most effective interventions for treating the diagnostic symptoms of autism. We employed a mouse model of autism to evaluate components of behavioral interventions that improve sociability in mice. BTBR T+tf/J (BTBR) is an inbred mouse strain that exhibits prominent behavioral phenotypes with face validity to all three diagnostic symptom categories of autism, including robust and well-replicated deficits in social approach and reciprocal social interactions. To investigate the role of peer interactions in the development of sociability, BTBR juvenile mice were reared in the same home cage with juvenile mice of a highly social inbred strain, C57BL/6J (B6). Subject mice were tested as young adults for sociability and repetitive behaviors. B6 controls reared with B6 showed their strain-typical high sociability. BTBR controls reared with BTBR showed their strain-typical lack of sociability. In contrast, BTBR reared with B6 as juveniles showed significant sociability as young adults. A 20-day intervention was as effective as a 40-day intervention for improving social approach behavior. High levels of repetitive self-grooming in BTBR were not rescued by peer-rearing with B6, indicating specificity of the intervention to the social domain. These results from a robust mouse model of autism support the interpretation that social enrichment with juvenile peers is a beneficial intervention for improving adult outcome in the social domain. This novel paradigm may prove useful for discovering factors that are essential for effective behavioral treatments, and biological mechanisms underlying effective behavioral interventions. En ligne : http://dx.doi.org/10.1002/aur.163 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] Social peers rescue autism-relevant sociability deficits in adolescent mice [Texte imprimé et/ou numérique] / Mu YANG, Auteur ; Kayla PERRY, Auteur ; Michael D. WEBER, Auteur ; Adam M. KATZ, Auteur ; Jacqueline N. CRAWLEY, Auteur . - 2011 . - p.17-27. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.17-27 Mots-clés : autism  BTBR inbred strain  mouse model  peer enrichment  social enrichment  behavioral intervention Index. décimale : PER Périodiques Résumé : Behavioral therapies are currently the most effective interventions for treating the diagnostic symptoms of autism. We employed a mouse model of autism to evaluate components of behavioral interventions that improve sociability in mice. BTBR T+tf/J (BTBR) is an inbred mouse strain that exhibits prominent behavioral phenotypes with face validity to all three diagnostic symptom categories of autism, including robust and well-replicated deficits in social approach and reciprocal social interactions. To investigate the role of peer interactions in the development of sociability, BTBR juvenile mice were reared in the same home cage with juvenile mice of a highly social inbred strain, C57BL/6J (B6). Subject mice were tested as young adults for sociability and repetitive behaviors. B6 controls reared with B6 showed their strain-typical high sociability. BTBR controls reared with BTBR showed their strain-typical lack of sociability. In contrast, BTBR reared with B6 as juveniles showed significant sociability as young adults. A 20-day intervention was as effective as a 40-day intervention for improving social approach behavior. High levels of repetitive self-grooming in BTBR were not rescued by peer-rearing with B6, indicating specificity of the intervention to the social domain. These results from a robust mouse model of autism support the interpretation that social enrichment with juvenile peers is a beneficial intervention for improving adult outcome in the social domain. This novel paradigm may prove useful for discovering factors that are essential for effective behavioral treatments, and biological mechanisms underlying effective behavioral interventions. En ligne : http://dx.doi.org/10.1002/aur.163 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118

Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions / Takeshi SAKURAI in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.28-39 Titre : Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions Type de document : Texte imprimé et/ou numérique Auteurs : Takeshi SAKURAI, Auteur ; Nathan P. DORR, Auteur ; Nagahide TAKAHASHI, Auteur ; L. Alison MCINNES, Auteur ; Gregory A. ELDER, Auteur ; Joseph D. BUXBAUM, Auteur Année de publication : 2011 Article en page(s) : p.28-39 Langues : Anglais (eng) Mots-clés : social behavior  intellectual disability  autism  mouse model Index. décimale : PER Périodiques Résumé : Identifying genes involved in social behavior is important for autism research. Williams–Beuren syndrome (WBS) is a developmental syndrome with unique neurocognitive features, including low IQ, deficits in visuospatial and visual-motor abilities, hypersensitivity to sounds, hypersociability, and increased general anxiety. The syndrome is caused by a recurrent hemizygous deletion of the 7q11.23 region, containing about 28 genes. One of genes in the region, GTF2I, has been implicated in the hypersociability and visuospatial deficits of WBS based on genotype–phenotype correlation studies of patients with atypical deletions. In order to clarify the involvement of GTF2I in neurocognitive function, especially social behavior, we have developed and characterized Gtf2i-deficient mice. We found that homozygous deletion of Gtf2i causes lethality during embryonic development with neural tube closure defects and exencephaly, consistent with other reports. Gtf2i heterozygous animals show no gross changes in brain structure or development. Furthermore, heterozygous animals show no alterations in learning and memory, including spatial memory as assessed by the Morris water maze, but show alterations in the recognition of novel objects. Interestingly, they show increased social interaction with unfamiliar mice and do not show typical social habituation processes, reminiscent of the hypersociability observed in WBS patients. The mice do not appear to show increased anxiety, supporting a specific effect of Gtf2i on defined domains of the WBS phenotype. These data indicate that Gtf2i is involved in several aspects of embryonic development and the development of social neurocircuitry and that GTF2I haploinsufficiency could be a contributor to the hypersociability in WBS patients. En ligne : http://dx.doi.org/10.1002/aur.169 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] Haploinsufficiency of Gtf2i, a gene deleted in Williams Syndrome, leads to increases in social interactions [Texte imprimé et/ou numérique] / Takeshi SAKURAI, Auteur ; Nathan P. DORR, Auteur ; Nagahide TAKAHASHI, Auteur ; L. Alison MCINNES, Auteur ; Gregory A. ELDER, Auteur ; Joseph D. BUXBAUM, Auteur . - 2011 . - p.28-39. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.28-39 Mots-clés : social behavior  intellectual disability  autism  mouse model Index. décimale : PER Périodiques Résumé : Identifying genes involved in social behavior is important for autism research. Williams–Beuren syndrome (WBS) is a developmental syndrome with unique neurocognitive features, including low IQ, deficits in visuospatial and visual-motor abilities, hypersensitivity to sounds, hypersociability, and increased general anxiety. The syndrome is caused by a recurrent hemizygous deletion of the 7q11.23 region, containing about 28 genes. One of genes in the region, GTF2I, has been implicated in the hypersociability and visuospatial deficits of WBS based on genotype–phenotype correlation studies of patients with atypical deletions. In order to clarify the involvement of GTF2I in neurocognitive function, especially social behavior, we have developed and characterized Gtf2i-deficient mice. We found that homozygous deletion of Gtf2i causes lethality during embryonic development with neural tube closure defects and exencephaly, consistent with other reports. Gtf2i heterozygous animals show no gross changes in brain structure or development. Furthermore, heterozygous animals show no alterations in learning and memory, including spatial memory as assessed by the Morris water maze, but show alterations in the recognition of novel objects. Interestingly, they show increased social interaction with unfamiliar mice and do not show typical social habituation processes, reminiscent of the hypersociability observed in WBS patients. The mice do not appear to show increased anxiety, supporting a specific effect of Gtf2i on defined domains of the WBS phenotype. These data indicate that Gtf2i is involved in several aspects of embryonic development and the development of social neurocircuitry and that GTF2I haploinsufficiency could be a contributor to the hypersociability in WBS patients. En ligne : http://dx.doi.org/10.1002/aur.169 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118

Modifying behavioral phenotypes in Fmr1KO mice: genetic background differences reveal autistic-like responses / Corinne M. SPENCER in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.40-56 Titre : Modifying behavioral phenotypes in Fmr1KO mice: genetic background differences reveal autistic-like responses Type de document : Texte imprimé et/ou numérique Auteurs : Corinne M. SPENCER, Auteur ; Olga ALEKSEYENKO, Auteur ; Shannon M. HAMILTON, Auteur ; Alexia M. THOMAS, Auteur ; Ekaterina SERYSHEVA, Auteur ; Lisa A. YUVA-PAYLOR, Auteur Année de publication : 2011 Article en page(s) : p.40-56 Langues : Anglais (eng) Mots-clés : fragile X syndrome  autism  genetic  behavior  animal model  mouse model Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in humans. In addition to cognitive impairment, patients may exhibit hyperactivity, attention deficits, social difficulties and anxiety, and autistic-like behaviors. The degree to which patients display these behaviors varies considerably and is influenced by family history, suggesting that genetic modifiers play a role in the expression of behaviors in FXS. Several studies have examined behavior in a mouse model of FXS in which the Fmr1 gene has been ablated. Most of those studies were done in Fmr1 knockout mice on a pure C57BL/6 or FVB strain background. To gain a better understanding of the effects of genetic background on behaviors resulting from the loss of Fmr1 gene expression, we generated F1 hybrid lines from female Fmr1 heterozygous mice on a pure C57BL/6J background bred with male Fmr1 wild-type (WT) mice of various background strains (A/J, DBA/2J, FVB/NJ, 129S1/SvImJ and CD-1). Male Fmr1 knockout and WT littermates from each line were examined in an extensive behavioral test battery. Results clearly indicate that multiple behavioral responses are dependent on genetic background, including autistic-like traits that are present on limited genetic backgrounds. This approach has allowed us to identify improved models for different behavioral symptoms present in FXS including autistic-like traits. En ligne : http://dx.doi.org/10.1002/aur.168 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] Modifying behavioral phenotypes in Fmr1KO mice: genetic background differences reveal autistic-like responses [Texte imprimé et/ou numérique] / Corinne M. SPENCER, Auteur ; Olga ALEKSEYENKO, Auteur ; Shannon M. HAMILTON, Auteur ; Alexia M. THOMAS, Auteur ; Ekaterina SERYSHEVA, Auteur ; Lisa A. YUVA-PAYLOR, Auteur . - 2011 . - p.40-56. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.40-56 Mots-clés : fragile X syndrome  autism  genetic  behavior  animal model  mouse model Index. décimale : PER Périodiques Résumé : Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in humans. In addition to cognitive impairment, patients may exhibit hyperactivity, attention deficits, social difficulties and anxiety, and autistic-like behaviors. The degree to which patients display these behaviors varies considerably and is influenced by family history, suggesting that genetic modifiers play a role in the expression of behaviors in FXS. Several studies have examined behavior in a mouse model of FXS in which the Fmr1 gene has been ablated. Most of those studies were done in Fmr1 knockout mice on a pure C57BL/6 or FVB strain background. To gain a better understanding of the effects of genetic background on behaviors resulting from the loss of Fmr1 gene expression, we generated F1 hybrid lines from female Fmr1 heterozygous mice on a pure C57BL/6J background bred with male Fmr1 wild-type (WT) mice of various background strains (A/J, DBA/2J, FVB/NJ, 129S1/SvImJ and CD-1). Male Fmr1 knockout and WT littermates from each line were examined in an extensive behavioral test battery. Results clearly indicate that multiple behavioral responses are dependent on genetic background, including autistic-like traits that are present on limited genetic backgrounds. This approach has allowed us to identify improved models for different behavioral symptoms present in FXS including autistic-like traits. En ligne : http://dx.doi.org/10.1002/aur.168 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118

Absence of preference for social novelty and increased grooming in integrin β3 knockout mice: Initial studies and future directions / Michelle D. CARTER in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.57-67 Titre : Absence of preference for social novelty and increased grooming in integrin β3 knockout mice: Initial studies and future directions Type de document : Texte imprimé et/ou numérique Auteurs : Michelle D. CARTER, Auteur ; Charisma R. SHAH, Auteur ; Christopher L. MULLER, Auteur ; Jacqueline N. CRAWLEY, Auteur ; Ana M.D. CARNEIRO, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur Année de publication : 2011 Article en page(s) : p.57-67 Langues : Anglais (eng) Mots-clés : autism  genetic  integrin  cell adhesion  serotonin  social memory  grooming  obsessive–compulsive disorder Index. décimale : PER Périodiques Résumé : Elevated whole blood serotonin 5-HT, or hyperserotonemia, is a common biomarker in autism spectrum disorder (ASD). The integrin β3 receptor subunit gene (ITGB3) is a quantitative trait locus for whole blood 5-HT levels. Recent work shows that integrin β3 interacts with the serotonin transporter (SERT) in both platelets and in the midbrain. Furthermore, multiple studies have now reported gene–gene interaction between the integrin β3 and SERT genes in association with ASD. Given the lack of previous data on the impact of integrin β3 on brain or behavioral phenotypes, we sought to compare mice with decreased or absent expression of the integrin β3 receptor subunit (Itgb3 + / − and −/ −) with wildtype littermate controls in behavioral tasks relevant to ASD. These mice did not show deficits in activity level in the open field or anxiety-like behavior on the elevated plus maze, two potential confounds in the evaluation of mouse social behavior. In the three-chamber social test, mice lacking integrin β3 were shown to have normal sociability but did not show a preference for social novelty. Importantly, the absence of integrin β3 did not impair olfaction or the ability to recall familiar social odors. Additionally, mice lacking integrin β3 showed increased grooming behavior in novel environments. These preliminary studies reveal altered social and repetitive behavior in these mice, which suggests that the integrin β3 subunit may be involved in brain systems relevant to ASD. Further work is needed to fully characterize these behavioral changes and the underlying brain mechanisms. En ligne : http://dx.doi.org/10.1002/aur.180 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] Absence of preference for social novelty and increased grooming in integrin β3 knockout mice: Initial studies and future directions [Texte imprimé et/ou numérique] / Michelle D. CARTER, Auteur ; Charisma R. SHAH, Auteur ; Christopher L. MULLER, Auteur ; Jacqueline N. CRAWLEY, Auteur ; Ana M.D. CARNEIRO, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur . - 2011 . - p.57-67. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.57-67 Mots-clés : autism  genetic  integrin  cell adhesion  serotonin  social memory  grooming  obsessive–compulsive disorder Index. décimale : PER Périodiques Résumé : Elevated whole blood serotonin 5-HT, or hyperserotonemia, is a common biomarker in autism spectrum disorder (ASD). The integrin β3 receptor subunit gene (ITGB3) is a quantitative trait locus for whole blood 5-HT levels. Recent work shows that integrin β3 interacts with the serotonin transporter (SERT) in both platelets and in the midbrain. Furthermore, multiple studies have now reported gene–gene interaction between the integrin β3 and SERT genes in association with ASD. Given the lack of previous data on the impact of integrin β3 on brain or behavioral phenotypes, we sought to compare mice with decreased or absent expression of the integrin β3 receptor subunit (Itgb3 + / − and −/ −) with wildtype littermate controls in behavioral tasks relevant to ASD. These mice did not show deficits in activity level in the open field or anxiety-like behavior on the elevated plus maze, two potential confounds in the evaluation of mouse social behavior. In the three-chamber social test, mice lacking integrin β3 were shown to have normal sociability but did not show a preference for social novelty. Importantly, the absence of integrin β3 did not impair olfaction or the ability to recall familiar social odors. Additionally, mice lacking integrin β3 showed increased grooming behavior in novel environments. These preliminary studies reveal altered social and repetitive behavior in these mice, which suggests that the integrin β3 subunit may be involved in brain systems relevant to ASD. Further work is needed to fully characterize these behavioral changes and the underlying brain mechanisms. En ligne : http://dx.doi.org/10.1002/aur.180 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118

The autism risk genes MET and PLAUR differentially impact cortical development / Kathie L. EAGLESON in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.68-83 Titre : The autism risk genes MET and PLAUR differentially impact cortical development Type de document : Texte imprimé et/ou numérique Auteurs : Kathie L. EAGLESON, Auteur ; Daniel B. CAMPBELL, Auteur ; Barbara L. THOMPSON, Auteur ; Mica Y. BERGMAN, Auteur ; Pat LEVITT, Auteur Année de publication : 2011 Article en page(s) : p.68-83 Langues : Anglais (eng) Mots-clés : animal models  developmental neurobiology  neuroanatomy Index. décimale : PER Périodiques Résumé : Candidate risk genes for autism spectrum disorder (ASD) have been identified, but the challenge of determining their contribution to pathogenesis remains. We previously identified two ASD risk genes encoding the receptor tyrosine kinase MET and the urokinase plasminogen activator receptor (PLAUR), which is thought to modulate availability of the MET ligand. We also reported a role for Met signaling in cortical interneuron development in vitro and a reduction of these neurons in uPAR (mouse ortholog of PLAUR) null mice, suggesting that disruption of either gene impacts cortical development similarly. Here, we modify this conclusion, reporting that interneuron numbers are unchanged in the neocortex of Metfx/fx/ Dlx5/6cre mice, in which Met is ablated from cells arising from the ventral telencephalon (VTel). Consistent with this, Met transcript is not detected in the VTel during interneuron genesis and migration; furthermore, during the postnatal period of interneuron maturation, Met is co-expressed in glutamatergic projection neurons, but not interneurons. Low levels of Met protein are expressed in the VTel at E12.5 and E14.5, likely reflecting the arrival of Met containing corticofugal axons. Met expression, however, is induced in E12.5 VTel cells after 2 days in vitro, perhaps underlying discrepancies between observations in vitro and in Metfx/fx/ Dlx5/6cre mice. We suggest that, in vivo, Met impacts the development of cortical projection neurons, whereas uPAR influences interneuron maturation. An altered balance between excitation and inhibition has been postulated as a biological mechanism for ASD; this imbalance could arise from different risk genes differentially affecting either or both elements. En ligne : http://dx.doi.org/10.1002/aur.172 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] The autism risk genes MET and PLAUR differentially impact cortical development [Texte imprimé et/ou numérique] / Kathie L. EAGLESON, Auteur ; Daniel B. CAMPBELL, Auteur ; Barbara L. THOMPSON, Auteur ; Mica Y. BERGMAN, Auteur ; Pat LEVITT, Auteur . - 2011 . - p.68-83. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.68-83 Mots-clés : animal models  developmental neurobiology  neuroanatomy Index. décimale : PER Périodiques Résumé : Candidate risk genes for autism spectrum disorder (ASD) have been identified, but the challenge of determining their contribution to pathogenesis remains. We previously identified two ASD risk genes encoding the receptor tyrosine kinase MET and the urokinase plasminogen activator receptor (PLAUR), which is thought to modulate availability of the MET ligand. We also reported a role for Met signaling in cortical interneuron development in vitro and a reduction of these neurons in uPAR (mouse ortholog of PLAUR) null mice, suggesting that disruption of either gene impacts cortical development similarly. Here, we modify this conclusion, reporting that interneuron numbers are unchanged in the neocortex of Metfx/fx/ Dlx5/6cre mice, in which Met is ablated from cells arising from the ventral telencephalon (VTel). Consistent with this, Met transcript is not detected in the VTel during interneuron genesis and migration; furthermore, during the postnatal period of interneuron maturation, Met is co-expressed in glutamatergic projection neurons, but not interneurons. Low levels of Met protein are expressed in the VTel at E12.5 and E14.5, likely reflecting the arrival of Met containing corticofugal axons. Met expression, however, is induced in E12.5 VTel cells after 2 days in vitro, perhaps underlying discrepancies between observations in vitro and in Metfx/fx/ Dlx5/6cre mice. We suggest that, in vivo, Met impacts the development of cortical projection neurons, whereas uPAR influences interneuron maturation. An altered balance between excitation and inhibition has been postulated as a biological mechanism for ASD; this imbalance could arise from different risk genes differentially affecting either or both elements. En ligne : http://dx.doi.org/10.1002/aur.172 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118

Lay abstracts in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.84-86 Titre : Lay abstracts Type de document : Texte imprimé et/ou numérique Année de publication : 2011 Article en page(s) : p.84-86 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.181 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] Lay abstracts [Texte imprimé et/ou numérique] . - 2011 . - p.84-86. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.84-86 Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.181 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118

International Society for Autism Research News in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.87 Titre : International Society for Autism Research News Type de document : Texte imprimé et/ou numérique Année de publication : 2011 Article en page(s) : p.87 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.190 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] International Society for Autism Research News [Texte imprimé et/ou numérique] . - 2011 . - p.87. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.87 Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.190 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118

The International Meeting for Autism Research in Autism Research, 4-1 (February 2011)  

Public ISBD [article]  inAutism Research > 4-1 (February 2011) . - p.88 Titre : The International Meeting for Autism Research Type de document : Texte imprimé et/ou numérique Année de publication : 2011 Article en page(s) : p.88 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.182 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118 [article] The International Meeting for Autism Research [Texte imprimé et/ou numérique] . - 2011 . - p.88. Langues : Anglais (eng) in Autism Research > 4-1 (February 2011) . - p.88 Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.182 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=118