The Sleep Disorder Canine Narcolepsy Is Caused by a Mutation in the Hypocretin (Orexin) Receptor 2 Gene
Open accessAbstract
Narcolepsy is a disabling sleep disorder affecting humans and animals. It is characterized by daytime sleepiness, cataplexy, and striking transitions from wakefulness into rapid eye movement (REM) sleep. In this study, we used positional cloning to identify an autosomal recessive mutation responsible for this sleep disorder in a well-established canine model. We have determined that canine narcolepsy is caused by disruption of the hypocretin (orexin) receptor 2 gene (Hcrtr2). This result identifies hypocretins as major sleep-modulating neurotransmitters and opens novel potential therapeutic approaches for narcoleptic patients.
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Without orexin or with altered orexin receptors, humans and animals experience narcolepsy.
“Without orexin or with altered orexin receptors, humans and animals experience narcolepsy,34–39”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [35]
Orexin neurons are both necessary and sufficient for wakefulness.
“Orexin neurons are both necessary and sufficient for wakefulness.”
From Effects of Traumatic Brain Injury on the Orexin/Hypocretin System (2025) · cites this paper as [35]
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- Authors
- Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers, W., Lin, X., Qiu, X., de Jong, P. J., Nishino, S., & Mignot, E.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Mignot, Emmanuel
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1999-08
- Volume
- 98
- Issue
- 3
- Pages
- 365-376
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2169378022
- Cited by
- 2,613
- References
- 2
- Citations by year
- 2026: 33 · 2025: 56 · 2024: 67 · 2023: 65 · 2022: 77 · 2021: 64 · 2020: 63 · 2019: 64 · 2018: 85 · 2017: 87 · 2016: 97 · 2015: 98 · 2014: 107 · 2013: 122 · 2012: 111
- FWCI
- 65.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1r01hl059601-01)
- National Heart, Lung, and Blood Institute (HL59601)
- National Institute of Neurological Disorders and Stroke (NS-23724, NS 33797)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- hypocretin receptor 2, orexin, positional cloning, autosomal recessive mutation, sleep regulation, REM sleep, cataplexy
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Chromosome Mapping, Dog Diseases, Dogs, Genes, Recessive, Genetic Markers, Humans, Karyotyping, Molecular Sequence Data, Narcolepsy, Sequence Homology, Nucleic Acid, Sleep, REM, Gene Library, Sequence Alignment, Sequence Homology, Amino Acid, In Situ Hybridization, Fluorescence, Receptors, Neuropeptide, Receptors, G-Protein-Coupled, Rats, Orexin Receptors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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