The Sleep Disorder Canine Narcolepsy Is Caused by a Mutation in the Hypocretin (Orexin) Receptor 2 Gene

Cell. 1999 Aug 6;98(3):365-76. doi: 10.1016/s0092-8674(00)81965-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chromosome Mapping*
  • Dog Diseases / genetics*
  • Dog Diseases / physiopathology
  • Dogs / genetics*
  • Gene Library
  • Genes, Recessive
  • Genetic Markers
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Molecular Sequence Data
  • Narcolepsy / genetics
  • Narcolepsy / physiopathology
  • Narcolepsy / veterinary*
  • Orexin Receptors
  • Rats
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide / chemistry
  • Receptors, Neuropeptide / genetics*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Sleep, REM / genetics

Substances

  • Genetic Markers
  • HCRTR2 protein, human
  • Hcrtr2 protein, rat
  • Orexin Receptors
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide

Associated data

  • GENBANK/AF164626