Title
Forward-genetics analysis of sleep in randomly mutagenized mice.
Document Type
Article
Publication Date
11-17-2016
JAX Source
Nature 2016 Nov 17; 539(7629):378-383
Volume
539
Issue
7629
First Page
378
Last Page
383
ISSN
1476-4687
PMID
27806374
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. Nature 2016 Nov 17; 539(7629):378-383.
Recommended Citation
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 S,
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 J,
Yanagisawa M.
Forward-genetics analysis of sleep in randomly mutagenized mice. Nature 2016 Nov 17; 539(7629):378-383