Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation

Richard M. Chemelli, Jon T. Willie, Christopher M. Sinton, Joel K Elmquist, Thomas Scammell, Charlotte Lee, James A Richardson, S. Clay Williams, Yumei Xiong, Yaz Kisanuki, Thomas E. Fitch, Masamitsu Nakazato, Robert E Hammer, Clifford B. Saper, Masashi Yanagisawa

Research output: Contribution to journalArticle

2308 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)437-451
Number of pages15
JournalCell
Volume98
Issue number4
DOIs
StatePublished - Aug 20 1999

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Narcolepsy
Knockout Mice
Molecular Biology
Sleep
Neurons
Lateral Hypothalamic Area
Eye movements
Wakefulness
REM Sleep
Neurology
Neuropeptides
Axons
Central Nervous System
Dogs
Phenotype
Pharmaceutical Preparations
Genetics

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Narcolepsy in orexin knockout mice : Molecular genetics of sleep regulation. / Chemelli, Richard M.; Willie, Jon T.; Sinton, Christopher M.; Elmquist, Joel K; Scammell, Thomas; Lee, Charlotte; Richardson, James A; Clay Williams, S.; Xiong, Yumei; Kisanuki, Yaz; Fitch, Thomas E.; Nakazato, Masamitsu; Hammer, Robert E; Saper, Clifford B.; Yanagisawa, Masashi.

In: Cell, Vol. 98, No. 4, 20.08.1999, p. 437-451.

Research output: Contribution to journalArticle

Chemelli, RM, Willie, JT, Sinton, CM, Elmquist, JK, Scammell, T, Lee, C, Richardson, JA, Clay Williams, S, Xiong, Y, Kisanuki, Y, Fitch, TE, Nakazato, M, Hammer, RE, Saper, CB & Yanagisawa, M 1999, 'Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation', Cell, vol. 98, no. 4, pp. 437-451. https://doi.org/10.1016/S0092-8674(00)81973-X
Chemelli RM, Willie JT, Sinton CM, Elmquist JK, Scammell T, Lee C et al. Narcolepsy in orexin knockout mice: Molecular genetics of sleep regulation. Cell. 1999 Aug 20;98(4):437-451. https://doi.org/10.1016/S0092-8674(00)81973-X
Chemelli, Richard M. ; Willie, Jon T. ; Sinton, Christopher M. ; Elmquist, Joel K ; Scammell, Thomas ; Lee, Charlotte ; Richardson, James A ; Clay Williams, S. ; Xiong, Yumei ; Kisanuki, Yaz ; Fitch, Thomas E. ; Nakazato, Masamitsu ; Hammer, Robert E ; Saper, Clifford B. ; Yanagisawa, Masashi. / Narcolepsy in orexin knockout mice : Molecular genetics of sleep regulation. In: Cell. 1999 ; Vol. 98, No. 4. pp. 437-451.
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