A genetic analysis of REM sleep based on a novel sleep related gene Nalcn

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18966
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: University of Tsukuba
• Principal Investigator: FUJIYAMA Tomoyuki 筑波大学, 国際統合睡眠医科学研究機構, 特別研究員(PD) (00635089)
• Co-Investigator(Renkei-kenkyūsha): KANDA Takeshi 筑波大学, 国際統合睡眠医科学研究機構(WPI-IIIS), 助教 (00599821) ; MIYOSHI Chika 筑波大学, 国際統合睡眠医科学研究機構(WPI-IIIS), 助教 (60613437) ; FUNATO Hiromasa 筑波大学, 国際統合睡眠医科学研究機構(WPI-IIIS), 客員教授 (90363118) ; YANAGISAWA Masashi 筑波大学, 国際統合睡眠医科学研究機構(WPI-IIIS), 教授/機構長 (20202369)
• Research Collaborator: MIZUNO Seiya 筑波大学, 生命科学動物資源センター(LARC), 助教 (10633141) ; TAKAHASHI Satoru 筑波大学, 生命科学動物資源センター(LARC), 教授 (50271896)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: レム睡眠 / Forward genetics / CRISPR / ENU mutagenesis / Dreamless / Nalcn / REM sleep

Outline of Final Research Achievements

Dreamless mice, which was established from an ENU mutagenized mouse, showed a decreased rapid-eye-movement (REM) sleep. Subsequent genome sequencing including whole exome sequencing and genetic linkage analysis revealed that the mutation in Dreamless mice affects a gene Nalcn, which codes for an ion-channel protein and has previously been implicated in the circadian control of the neuronal excitability. In addition, Funato and Fujiyama et al. demonstrated that the reproduction of the same mutation in Dreamless mice via CRISPR/Cas9 system could recapiturate thier phenotypes, which defined the causality of Dreamless mice. Electrophysiologically assessed brain waves were altered in Dreamless mutant mice compared with controls, during REM and NREM sleep, and during wakefulness. These findings implied that a novel sleep related gene Nalcn is involved in the regulation of all vigilance states, but especially in REM sleep.

Free Research Field

睡眠医科学