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 |
Section | 一般 |
Research Field |
Basic / Social brain science
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Research Institution | Shinshu University |
Principal Investigator |
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Project Period (FY) |
2013-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2014: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2013: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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Keywords | Neurexin / 自閉症 / シナプス / Neuroligin / ニューレキシン / ニューロリギン / マウスモデル |
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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Report
(5 results)
Research Products
(20 results)
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[Journal Article] Fluorescent protein tagging of endogenous protein in brain neurons using CRISPR/Cas9-mediated knock-in and in utero electroporation techniques.2016
Author(s)
Uemura T, Mori T, Kurihara T, Kawase S, Koike R, Satoga M, Cao X, Li X, Yanagawa T, Sakurai T, Shindo T, Tabuchi K.
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Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 35861-35861
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] β-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling.2015
Author(s)
Anderson GR, Aoto J, Tabuchi K, Foldy C, Covy J, Yee AX, Wu D, Lee SJ, Chen L, Malenka RC, Sudhof TC.
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Journal Title
Cell
Volume: 162(3)
Issue: 3
Pages: 593-606
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] PTPσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission.2015
Author(s)
Ko JS, Pramanik G, Um JW, Shim JS, Lee D, Kim KH, Chung GY, Condomitti G, Kim HM, Kim H, de Wit J, Park KS, Tabuchi K, Ko J.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 112(6)
Issue: 6
Pages: 1874-1879
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Enhanced synapse remodeling as a common phenotype in mouse models of autism.2014
Author(s)
Isshiki, M., Tanaka, S., Kuriu, T., Tabuchi, K., Takumi, T. and Okabe, S.
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Journal Title
Nat. Commun.
Volume: 5
Issue: 1
Pages: 4742-4742
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Calsyntenins function as synaptogenic adhesion molecules in concert with neurexins2014
Author(s)
Um, J. W. Pramanik, G. Ko, J. S. Song, M. Y. Lee, D. Kim, H. Park, K. S. Sudhof, T. C. Tabuchi, K. Ko, J.
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Journal Title
Cell Rep
Volume: 6(6)
Pages: 1096-1109
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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