PMID- 10481909
OWN - NLM
STAT- MEDLINE
DCOM- 19990923
LR  - 20190705
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 98
IP  - 4
DP  - 1999 Aug 20
TI  - Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation.
PG  - 437-51
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.
FAU - Chemelli, R M
AU  - Chemelli RM
AD  - Howard Hughes Medical Institute, Department of Molecular Genetics, University of 
      Texas Southwestern Medical Center at Dallas, 75235-9050, USA.
FAU - Willie, J T
AU  - Willie JT
FAU - Sinton, C M
AU  - Sinton CM
FAU - Elmquist, J K
AU  - Elmquist JK
FAU - Scammell, T
AU  - Scammell T
FAU - Lee, C
AU  - Lee C
FAU - Richardson, J A
AU  - Richardson JA
FAU - Williams, S C
AU  - Williams SC
FAU - Xiong, Y
AU  - Xiong Y
FAU - Kisanuki, Y
AU  - Kisanuki Y
FAU - Fitch, T E
AU  - Fitch TE
FAU - Nakazato, M
AU  - Nakazato M
FAU - Hammer, R E
AU  - Hammer RE
FAU - Saper, C B
AU  - Saper CB
FAU - Yanagisawa, M
AU  - Yanagisawa M
LA  - eng
GR  - DK53301/DK/NIDDK NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Carrier Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Orexin Receptors)
RN  - 0 (Orexins)
RN  - 0 (Protein Precursors)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Receptors, Neuropeptide)
RN  - R3UK8X3U3D (Modafinil)
SB  - IM
CIN - Cell. 1999 Aug 20;98(4):409-12. PMID: 10481905
MH  - Age of Onset
MH  - Animals
MH  - Benzhydryl Compounds/pharmacology/therapeutic use
MH  - Carrier Proteins/genetics/*metabolism/physiology
MH  - *Disease Models, Animal
MH  - Dog Diseases/genetics
MH  - Dogs
MH  - Electroencephalography
MH  - Electromyography
MH  - Humans
MH  - Hypothalamus/drug effects/physiopathology
MH  - *Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Modafinil
MH  - Narcolepsy/drug therapy/*genetics/metabolism/physiopathology/veterinary
MH  - Neurons/drug effects/pathology
MH  - Neuropeptides/*deficiency/genetics/*metabolism/physiology
MH  - Orexin Receptors
MH  - Orexins
MH  - Phenotype
MH  - Posture
MH  - Protein Precursors/*deficiency/genetics
MH  - Receptors, G-Protein-Coupled
MH  - Receptors, Neuropeptide/deficiency/genetics
MH  - Sleep/physiology
MH  - Sleep, REM/physiology
MH  - Species Specificity
MH  - Stereotyped Behavior
EDAT- 1999/09/11 00:00
MHDA- 1999/09/11 00:01
CRDT- 1999/09/11 00:00
PHST- 1999/09/11 00:00 [pubmed]
PHST- 1999/09/11 00:01 [medline]
PHST- 1999/09/11 00:00 [entrez]
AID - S0092-8674(00)81973-X [pii]
AID - 10.1016/s0092-8674(00)81973-x [doi]
PST - ppublish
SO  - Cell. 1999 Aug 20;98(4):437-51. doi: 10.1016/s0092-8674(00)81973-x.