Transcriptional Repressor DEC2 Regulates Sleep Length in Mammals

• Published in: Science (American Association for the Advancement of Science) Vol. 325; no. 5942; pp. 866 - 870
• Main Authors: He, Ying, Jones, Christopher R, Fujiki, Nobuhiro, Xu, Ying, Guo, Bin, Holder, Jimmy L. Jr, Rossner, Moritz J, Nishino, Seiji, Fu, Ying-Hui
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 14.08.2009; The American Association for the Advancement of Science
• Subjects: Activity Cycles - genetics; Adolescent; Adult; Aged; Amino Acid Sequence; Amino Acid Substitution; Animal models; Animals; Animals, Genetically Modified; Basic Helix-Loop-Helix Transcription Factors - chemistry; Basic Helix-Loop-Helix Transcription Factors - genetics; Basic Helix-Loop-Helix Transcription Factors - physiology; Biological and medical sciences; Child; Circadian Rhythm - genetics; Drosophila - genetics; Electroencephalography; Electromyography; Female; Fundamental and applied biological sciences. Psychology; Genetic mutation; Genotype & phenotype; Genotypes; Homeostasis; Humans; Male; Mice; Mice, Knockout; Mice, Transgenic; Middle Aged; Molecular Sequence Data; Mutation; Pedigree; Phenotypes; Point Mutation; Rapid eye movement sleep; Rodents; Sleep; Sleep - genetics; Sleep - physiology; Sleep Deprivation; Sleep, REM - genetics; Sleep, REM - physiology; Sleep. Vigilance; Transcription Factors - chemistry; Transcription Factors - genetics; Transcription Factors - physiology; Transgenic animals; Vertebrates: nervous system and sense organs; Wakefulness; Human; Animal model; Vigilance; Health; Rodentia; Transgenic animal; Homeostasis; Genotype; Vertebrata; Mammalia; Sleep; Mouse; Insomnia; Mutation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1174443

Sleep deprivation can impair human health and performance. Habitual total sleep time and homeostatic sleep response to sleep deprivation are quantitative traits in humans. Genetic loci for these traits have been identified in model organisms, but none of these potential animal models have a corresponding human genotype and phenotype. We have identified a mutation in a transcriptional repressor (hDEC2-P385R) that is associated with a human short sleep phenotype. Activity profiles and sleep recordings of transgenic mice carrying this mutation showed increased vigilance time and less sleep time than control mice in a zeitgeber time- and sleep deprivation-dependent manner. These mice represent a model of human sleep homeostasis that provides an opportunity to probe the effect of sleep on human physical and mental health.