Evidence map›Paper›PMID 27806374›Full record

ArticleNature2016

Forward-genetics analysis of sleep in randomly mutagenized mice.

Hiromasa Funato, Chika Miyoshi, Tomoyuki Fujiyama, Takeshi Kanda, Makito Sato, Zhiqiang Wang, Jing Ma, Shin Nakane, Jun Tomita, Aya Ikkyu and 27 more

Abstract read
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
178citing papers in PubMed, 1 pooled it
16.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

178 citing papers in PubMed, 1 synthesis or guideline pooled it, 336 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. To sleep and dream: Unraveling narcolepsy.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Modeling the Exposome in Murine Cardiovascular Disease.JACC. Basic to translational science · 2026
    Review
  5. Emerging genetics of sleep and circadian disorders.Current opinion in pediatrics · 2026
    Article
  6. Review
  7. Article
  8. Article
  9. Active zone plasticity couples sleep need to presynaptic hypophosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Current Evidence for Sleep States inCurrent sleep medicine reports · 2026
    Review
  15. Sleep regulation inFrontiers in neuroscience · 2026
    Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

118 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors at 10 institutions in 2 countries.

Hiromasa FunatoInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Chika MiyoshiInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Tomoyuki FujiyamaInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Takeshi KandaInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Makito SatoInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Zhiqiang WangInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Jing MaInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Shin NakaneDepartment of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan.
Jun TomitaDepartment of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan.
Aya IkkyuInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Miyo KakizakiInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Noriko Hotta-HirashimaInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Satomi KannoInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Haruna KomiyaInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Fuyuki AsanoInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Takato HondaInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Staci J KimInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Kanako HaranoInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Hiroki MuramotoInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Toshiya YonezawaInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Seiya MizunoLaboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Shinichi MiyazakiInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Linzi ConnorInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Vivek KumarDepartment of Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Ikuo MiuraTechnology and Development Team for Mouse Phenotype Analysis, RIKEN Bioresource Center, Tsukuba, Ibaraki 305-0074, Japan.
Tomohiro SuzukiTechnology and Development Team for Mouse Phenotype Analysis, RIKEN Bioresource Center, Tsukuba, Ibaraki 305-0074, Japan.
Atsushi WatanabeLaboratory of Research Advancement, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
Manabu AbeDepartment of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
Fumihiro SugiyamaLaboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Satoru TakahashiLaboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Kenji SakimuraDepartment of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata 951-8585, Japan.
Yu HayashiInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Qinghua LiuInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Kazuhiko KumeDepartment of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Aichi 467-8603, Japan.
Shigeharu WakanaTechnology and Development Team for Mouse Phenotype Analysis, RIKEN Bioresource Center, Tsukuba, Ibaraki 305-0074, Japan.
Joseph S TakahashiInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Masashi YanagisawaInternational Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
University of Tsukuba · JPTsukuba International University · JPNagoya City University · JPRIKEN BioResource Research Center · JPNiigata University · JPHoward Hughes Medical Institute · USJapan Science and Technology Agency · JPNational Center for Geriatrics and Gerontology · JPThe University of Texas Southwestern Medical Center · USToho University · JP

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Ann E. Rougvie · 2012 to 2026
$7.5M
Molecular Mechanisms of the RNAi/MicroRNA PathwaysR01GM111367 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI JIANG, QIU-XING, LIU, QINGHUA · 2015 to 2018
$1.4M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM111367NIH HHS GM111367NIH HHS P40 OD010440NIH Office of Research Infrastructure Programs P40 0D010440
6 · The paper itself

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.

Indexed as

MutagenesisMutationAmino Acid SequenceAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsConserved SequenceDrosophila melanogasterDrosophila ProteinsElectroencephalographyElectromyographyHomeostasisIon ChannelsMembrane ProteinsMiceNerve Tissue ProteinsCaenorhabditis elegans ProteinsDrosophila ProteinsIon ChannelsMembrane ProteinsNALCN protein, mouseNerve Tissue ProteinsProtein Serine-Threonine Kinasessalt-inducible kinase 3, Drosophilasik3 protein, C elegansSIK3 protein, mouse

Identifiers

PMID27806374
PMCPMC6076225
OpenAlexW2548868034

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.