Inactivation of the Catalytic Phosphatase Domain of PTPRT/RPTP? Increases Social Interaction in Mice / Keerthi THIRTAMARA RAJAMANI in Autism Research, 8-1 (February 2015)  

Public ISBD [article]  inAutism Research > 8-1 (February 2015) . - p.19-28 Titre : Inactivation of the Catalytic Phosphatase Domain of PTPRT/RPTP? Increases Social Interaction in Mice Type de document : Texte imprimé et/ou numérique Auteurs : Keerthi THIRTAMARA RAJAMANI, Auteur ; Brian O'NEILL, Auteur ; Dawn D. HAN, Auteur ; Adrienne FROSTHOLM, Auteur ; Andrej ROTTER, Auteur ; Howard H. GU, Auteur Article en page(s) : p.19-28 Langues : Anglais (eng) Mots-clés : PTPRT  RPTP?  social interaction  animal model Index. décimale : PER Périodiques Résumé : Receptor protein tyrosine phosphatase rho (RPTP?, gene symbol PTPRT) is a transmembrane protein expressed at high levels in the developing hippocampus, olfactory bulb, cortex, and cerebellum. It has an extracellular domain that interacts with other cell adhesion molecules, and it has two intracellular phosphatase domains, one of which is catalytically active. In a recent genome-wide association study, PTPRT was identified as a potential candidate gene for autism spectrum disorder (ASD) susceptibility. Mutation of a critical aspartate to alanine (D1046A) in the PTPRT catalytic domain inactivates phosphatase function but retains substrate binding. We have generated a knockin mouse line carrying the PTPRT D1046A mutation. The D1046A mutation in homozygous knockin mice did not significantly change locomotor activities or anxiety-related behaviors. In contrast, male homozygous mice had significantly higher social approach scores than wild-type animals. Our results suggest that PTPRT phosphatase function is important in modulating neural pathways involved in mouse social behaviors relevant to the symptoms in human ASD patients. Autism Res 2015, 8: 19–28. En ligne : http://dx.doi.org/10.1002/aur.1390 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=256 [article] Inactivation of the Catalytic Phosphatase Domain of PTPRT/RPTP? Increases Social Interaction in Mice [Texte imprimé et/ou numérique] / Keerthi THIRTAMARA RAJAMANI, Auteur ; Brian O'NEILL, Auteur ; Dawn D. HAN, Auteur ; Adrienne FROSTHOLM, Auteur ; Andrej ROTTER, Auteur ; Howard H. GU, Auteur . - p.19-28. Langues : Anglais (eng) in Autism Research > 8-1 (February 2015) . - p.19-28 Mots-clés : PTPRT  RPTP?  social interaction  animal model Index. décimale : PER Périodiques Résumé : Receptor protein tyrosine phosphatase rho (RPTP?, gene symbol PTPRT) is a transmembrane protein expressed at high levels in the developing hippocampus, olfactory bulb, cortex, and cerebellum. It has an extracellular domain that interacts with other cell adhesion molecules, and it has two intracellular phosphatase domains, one of which is catalytically active. In a recent genome-wide association study, PTPRT was identified as a potential candidate gene for autism spectrum disorder (ASD) susceptibility. Mutation of a critical aspartate to alanine (D1046A) in the PTPRT catalytic domain inactivates phosphatase function but retains substrate binding. We have generated a knockin mouse line carrying the PTPRT D1046A mutation. The D1046A mutation in homozygous knockin mice did not significantly change locomotor activities or anxiety-related behaviors. In contrast, male homozygous mice had significantly higher social approach scores than wild-type animals. Our results suggest that PTPRT phosphatase function is important in modulating neural pathways involved in mouse social behaviors relevant to the symptoms in human ASD patients. Autism Res 2015, 8: 19–28. En ligne : http://dx.doi.org/10.1002/aur.1390 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=256

Prenatal and Early-Life Exposure to High-Level Diesel Exhaust Particles Leads to Increased Locomotor Activity and Repetitive Behaviors in Mice / Keerthi THIRTAMARA RAJAMANI in Autism Research, 6-4 (August 2013)  

Public ISBD [article]  inAutism Research > 6-4 (August 2013) . - p.248-257 Titre : Prenatal and Early-Life Exposure to High-Level Diesel Exhaust Particles Leads to Increased Locomotor Activity and Repetitive Behaviors in Mice Type de document : Texte imprimé et/ou numérique Auteurs : Keerthi THIRTAMARA RAJAMANI, Auteur ; Shannon DOHERTY-LYONS, Auteur ; Crystal BOLDEN, Auteur ; Daniel WILLIS, Auteur ; Carol HOFFMAN, Auteur ; Judith ZELIKOFF, Auteur ; Lung-Chi CHEN, Auteur ; Howard GU, Auteur Article en page(s) : p.248-257 Langues : Anglais (eng) Mots-clés : diesel exhaust particles  early-life exposure  autism  repetitive behaviors Index. décimale : PER Périodiques Résumé : Abundant evidence indicates that both genetic and environmental factors contribute to the etiology of autism spectrum disorders (ASDs). However, limited knowledge is available concerning these contributing factors. An epidemiology study reported a link between increased incidence of autism and living closely to major highways, suggesting a possible role for pollutants from highway traffic. We investigated whether maternal exposure to diesel exhaust particles (DEP) negatively affects fetal development leading to autism-like phenotype in mice. Female mice and their offspring were exposed to DEP during pregnancy and nursing. Adult male offspring were then tested for behaviors reflecting the typical symptoms of ASD patients. Compared to control mice, DEP-exposed offspring exhibited higher locomotor activity, elevated levels of self-grooming in the presence of an unfamiliar mouse, and increased rearing behaviors, which may be relevant to the restricted and repetitive behaviors seen in ASD patients. However, the DEP-exposed mice did not exhibit deficits in social interactions or social communication which are the key features of ASD. These results suggest that early life exposure to DEP could have an impact on mouse development leading to observable changes in animal behaviors. Further studies are needed to reveal other environmental insults and genetic factors that would lead to animal models expressing key phenotypes of the autism spectrum disorders. En ligne : http://dx.doi.org/10.1002/aur.1287 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=212 [article] Prenatal and Early-Life Exposure to High-Level Diesel Exhaust Particles Leads to Increased Locomotor Activity and Repetitive Behaviors in Mice [Texte imprimé et/ou numérique] / Keerthi THIRTAMARA RAJAMANI, Auteur ; Shannon DOHERTY-LYONS, Auteur ; Crystal BOLDEN, Auteur ; Daniel WILLIS, Auteur ; Carol HOFFMAN, Auteur ; Judith ZELIKOFF, Auteur ; Lung-Chi CHEN, Auteur ; Howard GU, Auteur . - p.248-257. Langues : Anglais (eng) in Autism Research > 6-4 (August 2013) . - p.248-257 Mots-clés : diesel exhaust particles  early-life exposure  autism  repetitive behaviors Index. décimale : PER Périodiques Résumé : Abundant evidence indicates that both genetic and environmental factors contribute to the etiology of autism spectrum disorders (ASDs). However, limited knowledge is available concerning these contributing factors. An epidemiology study reported a link between increased incidence of autism and living closely to major highways, suggesting a possible role for pollutants from highway traffic. We investigated whether maternal exposure to diesel exhaust particles (DEP) negatively affects fetal development leading to autism-like phenotype in mice. Female mice and their offspring were exposed to DEP during pregnancy and nursing. Adult male offspring were then tested for behaviors reflecting the typical symptoms of ASD patients. Compared to control mice, DEP-exposed offspring exhibited higher locomotor activity, elevated levels of self-grooming in the presence of an unfamiliar mouse, and increased rearing behaviors, which may be relevant to the restricted and repetitive behaviors seen in ASD patients. However, the DEP-exposed mice did not exhibit deficits in social interactions or social communication which are the key features of ASD. These results suggest that early life exposure to DEP could have an impact on mouse development leading to observable changes in animal behaviors. Further studies are needed to reveal other environmental insults and genetic factors that would lead to animal models expressing key phenotypes of the autism spectrum disorders. En ligne : http://dx.doi.org/10.1002/aur.1287 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=212

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