| Project/Area Number |
17300099
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neuroscience in general
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| Research Institution | Niigata University |
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Principal Investigator |
SAKIMURA Kenji Niigata University, Department of Cellular Neurobiology, Professor (40162325)
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| Co-Investigator(Kenkyū-buntansha) |
ABE Manabu Niigata University, Department of Cellular Neurobiology Brain Research Institute, Assistant Professor (10334674)
YAMAZAKI Maya Brain Research Institute, Niigata University, Department of Cellular Neurobiology Brain Research Institute, Assistant Professor (70401768)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,200,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2007: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2006: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 2005: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | Conditional targeting / Glutamate receptor / TARP / C57BL / 6 / AD / HD / NMDA receptor / AMPA receptor / Synaptic targeting |
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| Research Abstract |
The aim of this project is to elucidate the molecular mechanism underlying the synaptic targeting and activity regulation of glutamate receptors, which are responsible for excitatory synapse transmission. For this purpose, we generated a series of foxed mouse strains for conditional knockout (KO) mice using the Cre/loxP recombination system. The targeted molecules were four AMPA-receptor subunits and their possibly auxiliary subunits, [○C]2, [○C]3, [○C]4, [○C]5, [○C]7 and[○C]8, which belong to the TARP[○C] molecules and are highly expressed in the brain. GluRε1 and GluRε2 subunits were also targeted in NMDA receptors. To generate flexed mice, we used our original ES-cell line RENKA, derived from C57BL/6 strain. Analysis of the TARP[○C]null KO mice showed that these molecules were crucial for the transfer of AMPA receptor to synapses and its stability, and that they were functioning as auxiliary subunits of AMPA receptors. When TARP[○C]8, which is distributed in telencephalon and highly expressed in hippocampal excitatory neurons, was lost, the KO mice showed impulsive and hyperactive phenomena, which improved with administration of antipsychotic drugs. Therefore, this KO mouse is thought to be an animal model for attention deficit hyperactivity disorder. The GluRε2 hippocampal CA3 selective-conditional KO mice indicated that GluRε2 was an essential subunit for NMDA receptor activity in this region.
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