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 in | Progress in neuro-psychopharmacology & biological psychiatry Vol. 84; no. Pt B; pp. 424 - 439 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
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. |
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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 givenname: J. surname: Luo fullname: Luo, J. – sequence: 2 givenname: R.H. surname: Norris fullname: Norris, R.H. – sequence: 3 givenname: S.L. surname: Gordon fullname: Gordon, S.L. – sequence: 4 givenname: J. surname: Nithianantharajah 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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Keywords | SAPAP SNAP25 GTP SAP Epilepsy STXBP1 Schizophrenia DLGAP − MAGUK Intellectual disability SV2A Magi-1 PTZ Y Syb Nlgn NSF PSD PRRT2 Behaviour Syt1 Syn + Syp Sytx Autism spectrum disorder Dnm1 Mouse models S-SCAM SHANK DLG Nrxn |
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