| First Author | Funato H | Year | 2016 |
| Journal | Nature | Volume | 539 |
| Issue | 7629 | Pages | 378-383 |
| PubMed ID | 27806374 | Mgi Jnum | J:236598 |
| Mgi Id | MGI:5806611 | Doi | 10.1038/nature20142 |
| Citation | Funato H, et al. (2016) Forward-genetics analysis of sleep in randomly mutagenized mice. Nature 539(7629):378-383 |
| abstractText | 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. |
