RRC ID 47237
著者 Funato H, Miyoshi C, Fujiyama T, Kanda T, Sato M, Wang Z, Ma J, Nakane S, Tomita J, Ikkyu A, Kakizaki M, Hotta-Hirashima N, Kanno S, Komiya H, Asano F, Honda T, Kim SJ, Harano K, Muramoto H, Yonezawa T, Mizuno S, Miyazaki S, Connor L, Kumar V, Miura I, Suzuki T, Watanabe A, Abe M, Sugiyama F, Takahashi S, Sakimura K, Hayashi Y, Liu Q, Kume K, Wakana S, Takahashi JS, Yanagisawa M.
タイトル Forward-genetics analysis of sleep in randomly mutagenized mice.
ジャーナル Nature
Abstract Sleep is conserved from invertebrates to vertebrates, and is tightly regulated in a homeostatic manner. The molecular and cellular mechanisms that determine the amount of rapid eye movement sleep (REMS) and non-REMS (NREMS) remain unknown. Here we identify two dominant mutations that affect sleep and wakefulness by using an electroencephalogram/electromyogram-based screen of randomly mutagenized mice. A splicing mutation in the Sik3 protein kinase gene causes a profound decrease in total wake time, owing to an increase in inherent sleep need. Sleep deprivation affects phosphorylation of regulatory sites on the kinase, suggesting a role for SIK3 in the homeostatic regulation of sleep amount. Sik3 orthologues also regulate sleep in fruitflies and roundworms. A missense, gain-of-function mutation in the sodium leak channel NALCN reduces the total amount and episode duration of REMS, apparently by increasing the excitability of REMS-inhibiting neurons. Our results substantiate the use of a forward-genetics approach for studying sleep behaviours in mice, and demonstrate the role of SIK3 and NALCN in regulating the amount of NREMS and REMS, respectively.
巻・号 539(7629)
ページ 378-383
公開日 2016-11-17
DOI 10.1038/nature20142
PII nature20142
PMID 27806374
PMC PMC6076225
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Conserved Sequence Drosophila Proteins / chemistry Drosophila Proteins / genetics Drosophila Proteins / metabolism Drosophila melanogaster / genetics Electroencephalography Electromyography Homeostasis / genetics Ion Channels / chemistry Ion Channels / genetics* Ion Channels / metabolism Membrane Proteins Mice Mutagenesis* Mutation* Nerve Tissue Proteins / chemistry Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism Neurons / metabolism Phosphorylation Protein Serine-Threonine Kinases / chemistry Protein Serine-Threonine Kinases / genetics* Protein Serine-Threonine Kinases / metabolism RNA Splicing / genetics Random Allocation Sleep / genetics* Sleep / physiology* Sleep Deprivation Sleep, REM / genetics Sleep, REM / physiology Time Factors Wakefulness / genetics Wakefulness / physiology
IF 42.779
引用数 82
WOS 分野 NEUROSCIENCES
リソース情報
ヒト・動物細胞 293(RCB1637) 293T(RCB2202)