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Cited by 3,095Sleep and Wakefulness ResearchNeuroscience of respiration and sleepCircadian rhythm and melatonin

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Narcolepsy in orexin Knockout Mice

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Chemelli, Richard M., Willie, Jon T., Sinton, Christopher M., Elmquist, Joel K., Scammell, Thomas, Lee, Charlotte, Richardson, James A., Williams, S.Clay, Xiong, Yumei, Kisanuki, Yaz, Fitch, Thomas E., Nakazato, Masamitsu, Hammer, Robert E., Saper, Clifford B., Yanagisawa, Masashi·1999·Cell
DOI 10.1016/s0092-8674(00)81973-x
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Abstract

Neurons containing the neuropeptide orexin (hypocretin) are located exclusively in the lateral hypothalamus and send axons to numerous regions throughout the central nervous system, including the major nuclei implicated in sleep regulation. Here, we report that, by behavioral and electroencephalographic criteria, orexin knockout mice exhibit a phenotype strikingly similar to human narcolepsy patients, as well as canarc-1 mutant dogs, the only known monogenic model of narcolepsy. Moreover, modafinil, an anti-narcoleptic drug with ill-defined mechanisms of action, activates orexin-containing neurons. We propose that orexin regulates sleep/wakefulness states, and that orexin knockout mice are a model of human narcolepsy, a disorder characterized primarily by rapid eye movement (REM) sleep dysregulation.

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Metadata

Authors
Chemelli, R. M., Willie, J. T., Sinton, C. M., Elmquist, J. K., Scammell, T., Lee, C., Richardson, J. A., Williams, S. C., Xiong, Y., Kisanuki, Y., Fitch, T. E., Nakazato, M., Hammer, R. E., Saper, C. B., & Yanagisawa, M.
Affiliations
  • Howard Hughes Medical Institute (US)
  • The University of Texas Southwestern Medical Center (US)
  • Beth Israel Deaconess Medical Center (US)
  • University of Miyazaki (JP)
Corresponding author
Yanagisawa, Masashi
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
1999-08
Volume
98
Issue
4
Pages
437-451
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/s0092-8674(00)81973-x
OpenAlex
W2072154498
Cited by
3,095
References
2
Citations by year
2026: 46 · 2025: 73 · 2024: 75 · 2023: 82 · 2022: 89 · 2021: 83 · 2020: 86 · 2019: 110 · 2018: 111 · 2017: 106 · 2016: 126 · 2015: 124 · 2014: 125 · 2013: 152 · 2012: 141
FWCI
67.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (DK53301)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Keywords
narcolepsy, orexin, orexin knockout mice, sleep regulation, REM sleep, sleep-wake behavior, modafinil, lateral hypothalamus
MeSH terms
Orexins, Modafinil, Animals, Benzhydryl Compounds, Carrier Proteins, Disease Models, Animal, Dog Diseases, Dogs, Electroencephalography, Electromyography, Humans, Hypothalamus, Male, Mice, Inbred C57BL, Narcolepsy, Neurons, Neuropeptides, Phenotype, Posture, Protein Precursors, Sleep, Sleep, REM, Species Specificity, Stereotyped Behavior, Age of Onset, Receptors, Neuropeptide, Mice, Knockout, Receptors, G-Protein-Coupled, Intracellular Signaling Peptides and Proteins, Mice, Orexin Receptors

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