TY - JOUR
T1 - Narcolepsy in orexin knockout mice
T2 - Molecular genetics of sleep regulation
AU - Chemelli, Richard M.
AU - Willie, Jon T.
AU - Sinton, Christopher M.
AU - Elmquist, Joel K
AU - Scammell, Thomas
AU - Lee, Charlotte
AU - Richardson, James A
AU - Clay Williams, S.
AU - Xiong, Yumei
AU - Kisanuki, Yaz
AU - Fitch, Thomas E.
AU - Nakazato, Masamitsu
AU - Hammer, Robert E
AU - Saper, Clifford B.
AU - Yanagisawa, Masashi
N1 - Funding Information:
We thank Mike Brown and Joe Goldstein for critical reading of the manuscript; Howard Gershenfeld and David Clouthier for helpful suggestions; and Shelley Dixon, Sahar Seyedkalal, Ivy Estabrooke, and Shan Maika for technical assistance. M. Y. is an Investigator and Y. K. is an Associate of the Howard Hughes Medical Institute. R. M. C. is an NIH fellow of the Pediatric Scientist Development Program. J. T. W. is an MSTP Fellow of the University of Texas Southwestern Medical Center. This work was supported in part by research grants from NIH (No. DK53301; J. K. E.), the Perot Family Foundation (M. Y.), the W. M. Keck Foundation (M. Y.), and Tanabe Medical Frontier Conference (M. Y.).
PY - 1999/8/20
Y1 - 1999/8/20
N2 - 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.
AB - 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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U2 - 10.1016/S0092-8674(00)81973-X
DO - 10.1016/S0092-8674(00)81973-X
M3 - Article
C2 - 10481909
AN - SCOPUS:0033588184
SN - 0092-8674
VL - 98
SP - 437
EP - 451
JO - Cell
JF - Cell
IS - 4
ER -