2016 Fiscal Year Final Research Report
Analysis of Neurexin mutant mice in which binding specificity of Neurexins to the ligands are manipulated to elucidate the molecular pathway responsible for autism.
| Project/Area Number |
25282242
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Basic / Social brain science
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Keywords | Neurexin / 自閉症 / シナプス / Neuroligin |
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| Outline of Final Research Achievements |
Neurexins are pre-synaptic cell adhesion molecules that bind post-synaptic Neuroligins to induce synapse formation and maturation. Both Neurexins and Neuroligins are implicated in autism. We hypothesized that the synaptic defects caused by disruption of Neurexins-Neuroligins interaction may be involved in the molecular pathophysiology of autism. To test this hypothesis, we generated mutant mice of Neurexins that have deficit of Neurexin-Neuroligin binding and analyzed the effect on synapse functions. Neurexin-3 ss4+ knockin mice of which Neurexin-3 lacks binding affinity to Neuroligins decreased the AMPA receptor-mediated synaptic transmission in the hippocampal neurons due to the hyper-internalization of AMPA receptor from the post-synapitc membrane. This phenotype is consistent with that in Neuroligin-3 R704C autism model mice, suggesting that this may be the mechanism caused by impaired Neurexin-Neuroligin interaction associated with autism pathophysiology.
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| Free Research Field |
神経生理学
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