Neurodevelopmental synaptopathies: Insights from behaviour in rodent models of synapse gene mutations

The genomic revolution has begun to unveil the enormous complexity and heterogeneity of the genetic basis of neurodevelopmental disorders such as such epilepsy, intellectual disability, autism spectrum disorder and schizophrenia. Increasingly, human mutations in synapse genes are being identified ac...

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Published inProgress in neuro-psychopharmacology & biological psychiatry Vol. 84; no. Pt B; pp. 424 - 439
Main Authors Luo, J., Norris, R.H., Gordon, S.L., Nithianantharajah, J.
Format Journal Article
LanguageEnglish
Published England Elsevier Inc 08.06.2018
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Abstract The genomic revolution has begun to unveil the enormous complexity and heterogeneity of the genetic basis of neurodevelopmental disorders such as such epilepsy, intellectual disability, autism spectrum disorder and schizophrenia. Increasingly, human mutations in synapse genes are being identified across these disorders. These neurodevelopmental synaptopathies highlight synaptic homeostasis pathways as a convergence point underlying disease mechanisms. Here, we review some of the key pre- and postsynaptic genes in which penetrant human mutations have been identified in neurodevelopmental disorders for which genetic rodent models have been generated. Specifically, we focus on the main behavioural phenotypes that have been documented in these animal models, to consolidate our current understanding of how synapse genes regulate key behavioural and cognitive domains. These studies provide insights into better understanding the basis of the overlapping genetic and cognitive heterogeneity observed in neurodevelopmental disorders. •Human mutations in pre- and postsynaptic genes impact multiple developmental disorders.•Behavioural and cognitive analysis of mouse genetic models reveal complex findings.•Requirement for standardisation of behavioural and cognitive assays and analyses.•Need for more comprehensive analysis of multiple behavioural and cognitive domains.
AbstractList The genomic revolution has begun to unveil the enormous complexity and heterogeneity of the genetic basis of neurodevelopmental disorders such as such epilepsy, intellectual disability, autism spectrum disorder and schizophrenia. Increasingly, human mutations in synapse genes are being identified across these disorders. These neurodevelopmental synaptopathies highlight synaptic homeostasis pathways as a convergence point underlying disease mechanisms. Here, we review some of the key pre- and postsynaptic genes in which penetrant human mutations have been identified in neurodevelopmental disorders for which genetic rodent models have been generated. Specifically, we focus on the main behavioural phenotypes that have been documented in these animal models, to consolidate our current understanding of how synapse genes regulate key behavioural and cognitive domains. These studies provide insights into better understanding the basis of the overlapping genetic and cognitive heterogeneity observed in neurodevelopmental disorders.
The genomic revolution has begun to unveil the enormous complexity and heterogeneity of the genetic basis of neurodevelopmental disorders such as such epilepsy, intellectual disability, autism spectrum disorder and schizophrenia. Increasingly, human mutations in synapse genes are being identified across these disorders. These neurodevelopmental synaptopathies highlight synaptic homeostasis pathways as a convergence point underlying disease mechanisms. Here, we review some of the key pre- and postsynaptic genes in which penetrant human mutations have been identified in neurodevelopmental disorders for which genetic rodent models have been generated. Specifically, we focus on the main behavioural phenotypes that have been documented in these animal models, to consolidate our current understanding of how synapse genes regulate key behavioural and cognitive domains. These studies provide insights into better understanding the basis of the overlapping genetic and cognitive heterogeneity observed in neurodevelopmental disorders. •Human mutations in pre- and postsynaptic genes impact multiple developmental disorders.•Behavioural and cognitive analysis of mouse genetic models reveal complex findings.•Requirement for standardisation of behavioural and cognitive assays and analyses.•Need for more comprehensive analysis of multiple behavioural and cognitive domains.
Author Nithianantharajah, J.
Norris, R.H.
Gordon, S.L.
Luo, J.
Author_xml – sequence: 1
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  fullname: Nithianantharajah, J.
  email: jess.n@florey.edu.au
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29217145$$D View this record in MEDLINE/PubMed
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SNAP25
GTP
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Epilepsy
STXBP1
Schizophrenia
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Intellectual disability
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Snippet The genomic revolution has begun to unveil the enormous complexity and heterogeneity of the genetic basis of neurodevelopmental disorders such as such...
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SubjectTerms Autism spectrum disorder
Behaviour
Epilepsy
Intellectual disability
Mouse models
Schizophrenia
Title Neurodevelopmental synaptopathies: Insights from behaviour in rodent models of synapse gene mutations
URI https://dx.doi.org/10.1016/j.pnpbp.2017.12.001
https://www.ncbi.nlm.nih.gov/pubmed/29217145
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