The Experts below are selected from a list of 306 Experts worldwide ranked by ideXlab platform
J. Peter H. Burbach - One of the best experts on this subject based on the ideXlab platform.
-
Contactins: structural aspects in relation to developmental functions in brain disease.
Advances in Protein Chemistry, 2020Co-Authors: Amila Zuko, Samuel Bouyain, Bert Van Der Zwaag, J. Peter H. BurbachAbstract:The contactins are members of a protein subfamily of neural immunoglobulin (Ig) domain-containing cell adhesion molecules. Their architecture is based on six N-terminal Ig domains, four fibronectin type III domains, and a C-terminal glycophosphatidylinositol (GPI)-anchor to the extracellular part of the cell membrane. Genetics of neuropsychiatric disorders, particularly autism spectrum disorders, have pinpointed contactin-4, -5, and -6 (CNTN4, -5, and -6) as potential disease genes in neurodevelopmental disorders and suggested that they participate in pathways important for appropriate brain development. These contactins have distinct but overlapping patterns of brain expression, and null-mutation causes subtle morphological and functional defects in the brain. The molecular basis of their neurodevelopmental functions is likely conferred by heterophilic protein interactions. CNTN4, -5, and -6 interact with protein tyrosine phosphatase receptor gamma (Ptptg) using a shared binding site that spans their second and third Ig repeats. Interactions with amyloid precursor protein (APP), Notch, and other IgCAMs have also been indicated. The present data indicate that CNTN4, -5, and -6 proteins may be part of heteromeric receptor complexes as well as serve as ligands themselves.
-
A current view on contactin-4, -5, and -6 : Implications in neurodevelopmental disorders
Molecular and Cellular Neuroscience, 2017Co-Authors: Asami Oguro-ando, Amila Zuko, Kristel T. E. Kleijer, J. Peter H. BurbachAbstract:Contactins (Cntns) are a six-member subgroup of the immunoglobulin cell adhesion molecule superfamily (IgCAMs) with pronounced brain expression and function. Recent genetic studies of neuropsychiatric disorders have pinpointed contactin-4 (CNTN4), contactin-5 (CNTN5) and contactin-6 (CNTN6) as candidate genes in neurodevelopmental disorders, particularly in autism spectrum disorders (ASDs), but also in intellectual disability, schizophrenia (SCZ), attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD), alcohol use disorder (AUD) and anorexia nervosa (AN). This suggests that they have important functions during neurodevelopment. This suggestion is supported by data showing that neurite outgrowth, cell survival and neural circuit formation can be affected by disruption of these genes. Here, we review the current genetic data about their involvement in neuropsychiatric disorders and explore studies on how null mutations affect mouse behavior. Finally, we highlight to role of protein–protein interactions in the potential mechanism of action of CNTN4, -5 and -6 and emphasize that complexes with other membrane proteins may play a role in neuronal developmental functions.
-
Limited impact of CNTN4 mutation on autism-related traits in developing and adult C57BL/6J mice
Journal of Neurodevelopmental Disorders, 2016Co-Authors: Remco T. Molenhuis, Hilgo Bruining, Esther Remmelink, Leonie De Visser, Maarten Loos, J. Peter H. BurbachAbstract:Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4 , one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 ( CNTN4 ) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages. Methods C57BL/6J mice with heterozygous and homozygous disruption of CNTN4 were studied through an extensive, partially longitudinal, test battery at various developmental stages, including various paradigms testing social and restricted repetitive behaviors. Results Developmental neurological and cognitive screenings revealed no significant differences between genotypes, and ASD-related behavioral domains were also unchanged in CNTN4 -deficient versus wild-type mice. The impact of CNTN4 -deficiency was found to be limited to increased startle responsiveness following auditory stimuli of different high amplitudes in heterozygous and homozygous CNTN4 -deficient mice and enhanced acquisition in a spatial learning task in homozygous mice. Conclusions Disruption of CNTN4 in the C57BL/6J background does not affect specific autism-related phenotypes in developing or adult mice but causes subtle non-disorder specific changes in sensory behavioral responses and cognitive performance.
-
Limited impact of CNTN4 mutation on autism-related traits in developing and adult C57BL/6J mice.
Journal of Neurodevelopmental Disorders, 2016Co-Authors: Remco T. Molenhuis, Hilgo Bruining, Esther Remmelink, Leonie De Visser, Maarten Loos, J. Peter H. BurbachAbstract:Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4, one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 (CNTN4) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages.
-
Contactins in the neurobiology of autism
European Journal of Pharmacology, 2013Co-Authors: Amila Zuko, Kristel T. E. Kleijer, Asami Oguro-ando, Emma Van Daalen, Bert Van Der Zwaag, J. Peter H. BurbachAbstract:Autism is a disease of brain plasticity. Inspiring work of Willem Hendrik Gispen on neuronal plasticity has stimulated us to investigate gene defects in autism and the consequences for brain development. The central process in the pathogenesis of autism is local dendritic mRNA translation which is dependent on axodendritic communication. Hence, most autism-related gene products (i) are part of the protein synthesis machinery itself, (ii) are components of the mTOR signal transduction pathway, or (iii) shape synaptic activity and plasticity. Accordingly, prototype drugs have been recognized that interfere with these pathways. The contactin (CNTN) family of Ig cell adhesion molecules (IgCAMs) harbours at least three members that have genetically been implicated in autism: CNTN4, CNTN5, and CNTN6. In this chapter we review the genetic and neurobiological data underpinning their role in normal and abnormal development of brain systems, and the consequences for behavior. Although data on each of these CNTNs are far from complete, we tentatively conclude that these three contactins play roles in brain development in a critical phase of establishing brain systems and their plasticity. They modulate neuronal activities, such as neurite outgrowth, synaptogenesis, survival, guidance of projections and terminal branching of axons in forming neural circuits. Current research on these CNTNs concentrate on the neurobiological mechanism of their developmental functions. A future task will be to establish if proposed pharmacological strategies to counteract ASD-related symptomes can also be applied to reversal of phenotypes caused by genetic defects in these CNTN genes.
Remco T. Molenhuis - One of the best experts on this subject based on the ideXlab platform.
-
Limited impact of CNTN4 mutation on autism-related traits in developing and adult C57BL/6J mice
Journal of Neurodevelopmental Disorders, 2016Co-Authors: Remco T. Molenhuis, Hilgo Bruining, Esther Remmelink, Leonie De Visser, Maarten Loos, J. Peter H. BurbachAbstract:Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4 , one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 ( CNTN4 ) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages. Methods C57BL/6J mice with heterozygous and homozygous disruption of CNTN4 were studied through an extensive, partially longitudinal, test battery at various developmental stages, including various paradigms testing social and restricted repetitive behaviors. Results Developmental neurological and cognitive screenings revealed no significant differences between genotypes, and ASD-related behavioral domains were also unchanged in CNTN4 -deficient versus wild-type mice. The impact of CNTN4 -deficiency was found to be limited to increased startle responsiveness following auditory stimuli of different high amplitudes in heterozygous and homozygous CNTN4 -deficient mice and enhanced acquisition in a spatial learning task in homozygous mice. Conclusions Disruption of CNTN4 in the C57BL/6J background does not affect specific autism-related phenotypes in developing or adult mice but causes subtle non-disorder specific changes in sensory behavioral responses and cognitive performance.
-
limited impact of CNTN4 mutation on autism related traits in developing and adult c57bl 6j mice
Journal of Neurodevelopmental Disorders, 2016Co-Authors: Remco T. Molenhuis, Hilgo Bruining, Esther Remmelink, Leonie De Visser, Maarten Loos, Peter J H BurbachAbstract:Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4, one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 (CNTN4) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages.
-
Limited impact of CNTN4 mutation on autism-related traits in developing and adult C57BL/6J mice.
Journal of Neurodevelopmental Disorders, 2016Co-Authors: Remco T. Molenhuis, Hilgo Bruining, Esther Remmelink, Leonie De Visser, Maarten Loos, J. Peter H. BurbachAbstract:Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4, one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 (CNTN4) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages.
Hilgo Bruining - One of the best experts on this subject based on the ideXlab platform.
-
Limited impact of CNTN4 mutation on autism-related traits in developing and adult C57BL/6J mice
Journal of Neurodevelopmental Disorders, 2016Co-Authors: Remco T. Molenhuis, Hilgo Bruining, Esther Remmelink, Leonie De Visser, Maarten Loos, J. Peter H. BurbachAbstract:Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4 , one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 ( CNTN4 ) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages. Methods C57BL/6J mice with heterozygous and homozygous disruption of CNTN4 were studied through an extensive, partially longitudinal, test battery at various developmental stages, including various paradigms testing social and restricted repetitive behaviors. Results Developmental neurological and cognitive screenings revealed no significant differences between genotypes, and ASD-related behavioral domains were also unchanged in CNTN4 -deficient versus wild-type mice. The impact of CNTN4 -deficiency was found to be limited to increased startle responsiveness following auditory stimuli of different high amplitudes in heterozygous and homozygous CNTN4 -deficient mice and enhanced acquisition in a spatial learning task in homozygous mice. Conclusions Disruption of CNTN4 in the C57BL/6J background does not affect specific autism-related phenotypes in developing or adult mice but causes subtle non-disorder specific changes in sensory behavioral responses and cognitive performance.
-
limited impact of CNTN4 mutation on autism related traits in developing and adult c57bl 6j mice
Journal of Neurodevelopmental Disorders, 2016Co-Authors: Remco T. Molenhuis, Hilgo Bruining, Esther Remmelink, Leonie De Visser, Maarten Loos, Peter J H BurbachAbstract:Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4, one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 (CNTN4) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages.
-
Limited impact of CNTN4 mutation on autism-related traits in developing and adult C57BL/6J mice.
Journal of Neurodevelopmental Disorders, 2016Co-Authors: Remco T. Molenhuis, Hilgo Bruining, Esther Remmelink, Leonie De Visser, Maarten Loos, J. Peter H. BurbachAbstract:Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4, one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 (CNTN4) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages.
Peter J H Burbach - One of the best experts on this subject based on the ideXlab platform.
-
heterogeneity of cell surface glutamate and gaba receptor expression in shank and CNTN4 autism mouse models
Frontiers in Molecular Neuroscience, 2018Co-Authors: Christopher Heise, Jonathan M Preuss, Jan C Schroeder, Chiara R Battaglia, Jonas Kolibius, Rebecca Schmid, Michael R Kreutz, Peter J H Burbach, Tobias M BoeckersAbstract:Autism spectrum disorder (ASD) refers to a large set of neurodevelopmental disorders, which have in common both repetitive behavior and abnormalities in social interactions and communication. Interestingly, most forms of ASD have a strong genetic contribution. However, the molecular underpinnings of this disorder remain elusive. The SHANK3 gene (and to a lesser degree SHANK2) which encode for the postsynaptic density (PSD) proteins SHANK3/SHANK2 and the CONTACTIN 4 gene which encodes for the neuronal glycoprotein CONTACTIN4 (CNTN4) exhibit mutated variants which are associated with ASD. Like many of the other genes associated with ASD, both SHANKs and CNTN4 affect synapse formation and function and are therefore related to the proper development and signaling capability of excitatory and inhibitory neuronal networks in the adult mammal brain. In this study we used mutant/knock-out mice of Shank2 (Shank2-/-), Shank3 (Shank3αβ-/-), and CNTN4 (CNTN4-/-) as ASD-models to explore whether these mice share a molecular signature in glutamatergic and GABAergic synaptic transmission in ASD-related brain regions. Using a biotinylation assay and subsequent western blotting we focused our analysis on cell surface expression of classical several ionotropic glutamate and GABA receptor subunits: GluA1, GluA2, and NR1GluN1 were analyzed for excitatory synaptic transmission, and the α1 subunit of the GABAA receptor was analyzed for inhibitory synaptic transmission. We found that both Shank2-/- and Shank3αβ-/- mice exhibit reduced levels of several cell surface glutamate receptors in most of the analyzed brain regions – especially in the striatum and thalamus – when compared to wildtype controls. Interestingly, even though CNTN4-/- mice also show reduced levels of some cell surface glutamate receptors in the cortex and hippocampus, increased levels of cell surface glutamate receptors were found in the striatum. Moreover, CNTN4-/- mice do not only show brain region-specific alterations in cell surface glutamate receptors but also a downregulation of cell surface GABA receptors in several of the analyzed brain regions. The results of this study suggest that even though mutations in defined genes can be associated with ASD this does not necessarily result in a common molecular phenotype in surface expression of glutamatergic and GABAergic receptor subunits in defined brain regions.
-
limited impact of CNTN4 mutation on autism related traits in developing and adult c57bl 6j mice
Journal of Neurodevelopmental Disorders, 2016Co-Authors: Remco T. Molenhuis, Hilgo Bruining, Esther Remmelink, Leonie De Visser, Maarten Loos, Peter J H BurbachAbstract:Background Mouse models offer an essential tool to unravel the impact of genetic mutations on autism-related phenotypes. The behavioral impact of some important candidate gene models for autism spectrum disorder (ASD) has not yet been studied, and existing characterizations mostly describe behavioral phenotypes at adult ages, disregarding the developmental nature of the disorder. In this context, the behavioral influence of CNTN4, one of the strongest suggested ASD candidate genes, is unknown. Here, we used our recently established developmental test battery to characterize the consequences of disruption of contactin 4 (CNTN4) on neurological, sensory, cognitive, and behavioral phenotypes across different developmental stages.
Hideshi Kawakami - One of the best experts on this subject based on the ideXlab platform.
-
the CNTN4 c 4256c t mutation is rare in japanese with inherited spinocerebellar ataxia
Journal of the Neurological Sciences, 2008Co-Authors: Eiji Tanaka, Hirofumi Maruyama, Hiroyuki Morino, Eiko Nakajima, Hideshi KawakamiAbstract:To confirm the incidence of SCA16 in Japan, we screened DNA samples from a number of patients of ataxia of unknown etiology for the substitution. We examined a total of 323 DNA samples from Japanese patients with inherited spinocerebellar ataxia. We found no 317-base pair band in the patients with ataxia of unknown etiology. It seemed that this mutation (c.4256C>T) is rare in Japanese patients with inherited spinocerebellar ataxia. Mutations in other populations should be analyzed. Pathological examinations and molecular biological examinations are needed to confirm that this mutation is a true cause of SCA16.
-
short communication the CNTN4 c 4256cnt mutation is rare in japanese with inherited spinocerebellar ataxia
2008Co-Authors: Eiji Tanaka, Hirofumi Maruyama, Hiroyuki Morino, Eiko Nakajima, Hideshi KawakamiAbstract:To confirm the incidence of SCA16 in Japan, we screened DNA samples from a number of patients of ataxia of unknown etiology for the substitution. We examined a total of 323 DNA samples from Japanese patients with inherited spinocerebellar ataxia. We found no 317-base pair band in the patients with ataxia of unknown etiology. It seemed that this mutation (c.4256CNT) is rare in Japanese patients with inherited spinocerebellar ataxia. Mutations in other populations should be analyzed. Pathological examinations and molecular biological examinations are needed to confirm that this mutation is a true cause of SCA16. © 2007 Elsevier B.V. All rights reserved.