| Project/Area Number |
18K14811
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 46010:Neuroscience-general-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
Fujiyama Tomoyuki 筑波大学, 国際統合睡眠医科学研究機構, 助教 (00635089)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | NALCN / レム睡眠 / CRISPR / 中枢神経系 / マウス / Dreamless / イオンチャネル / Nalcn / central nervous system / mouse / REM sleep |
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| Outline of Final Research Achievements |
Although sleep is a ubiquitous animal behavior, the molecular/neural basis mechanism of REM sleep (REMS) remains unknown. The single nucleotide change in Nalcn gene leads to a single amino acid substitution (N315K) of the gene product leak cation channel NALCN that we termed Dreamless which shows REMS abnormality. To elucidate where the NALCN in brain take effect on REMS regulation, we generated Nalcn mutant lines bearing flox or FLEx knock-in for loss-of- and gain-of-function studies, respectively. In Nalcn-FLEx mice, we observed that the mice with a systemic Cre-expressing line Actb-iCre showed Dreamless-like phenotype on the electroencephalogram and electromyogram (EEG/EMG) analysis. In Nalcn-flox mice, we confirmed the neuronal subtype-specific deletion of Nalcn mRNA expression in adult brain tissue. By using these two Nalcn gene mutant mouse lines, we got some preliminary data that the Nalcn in excitatory neuron, or telencephalon region, may play a role for REM sleep regulation.
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| Academic Significance and Societal Importance of the Research Achievements |
睡眠は、我々が日常的に経験し人生の三分の一の時間を費やす行為であるにもかかわらず、現在でも本質的な意義や機能、制御機構等が謎に包まれている。レム睡眠は記憶の固定化に重要であることが知られているが、Nalcn遺伝子に変異を持ちレム睡眠異常を示すDreamless変異マウスでは、記憶機能などにも異常が現れることは重要な点である。Nalcnをターゲットとして遺伝子改変マウスを精査することで、レム睡眠が関わる脳機能と関連のある新規の神経細胞群の特定につながることが期待される。
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