Narcolepsy

 

Gene: HCRTR2

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutations:

Dachshund mutation: Substitution, HCRTR2 gene; c.160 G>A, p.(E54K)

Doberman Pincher mutation: Insertion (splicing error), HCRTR2 gene; c.647-36_647-35 ins. 226 nt

Labrador Retriever mutation: Substitution (splicing error), HCRTR2 gene; c.1105+5 G>A

Medical system: Neurological

Breed: American Staffordshire Terrier/Amstaff, Dachshund Miniature Longhair/Shorthair, Dachshund Miniature Wirehair, Dachshund Standard Longhair/Shorthair, Doberman Pinscher, Labrador Retriever, Rottweiler, Schnauzer - Miniature

Age of onset of symptoms: Between 1 and 6 months

Narcolepsy is a sleep disorder found in several dog breeds including the Dachshund, Doberman Pincher and Labrador Retriever breeds.  This condition first becomes apparent between 1 and 6 months of age.  Affected dogs sleep much longer than normal and are generally less active than their normal littermates.  The most characteristic symptom of narcolepsy involves episodes of cataplexy, involving loss of muscle tone without initial loss of conciseness.  Episodes occur following a stimulating activity such as exercise or a meal and can last for several seconds to several minutes.  If the episode is prolonged, the dogs will often fall asleep.  The disease does not progress but affected animals will continue to have episodes throughout their lives.

 

References:

OMIA link: [0703-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Mondino A, Delucchi L, Moeser A, Cerdá-González S, Vanini G. (2021) Sleep disorders in dogs: A pathophysiological and clinical review. Top Companion Anim Med 43:100516. [pubmed/33556640]

Tisdale RK, Yamanaka A, Kilduff TS. (2021) Animal models of narcolepsy and the hypocretin/orexin system: Past, present, and future. Sleep 44(6):zsaa278. [pubmed/33313880]

Toth LA, Bhargava P. (2013) Animal models of sleep disorders. Comp Med 63:91-104, 2013. [pubmed/23582416]

Chen L, Brown RE, McKenna JT, McCarley RW. (2009) Animal models of narcolepsy.  CNS Neurol Disord Drug Targets 8(4):296-308.  [pubmed/19689311]

Tonokura M, Fujita K, Nishino S. (2007) Review of pathophysiology and clinical management of narcolepsy in dogs. Vet Rec 161:375-80. [pubmed/17873267]

Hungs M, Fan J, Lin L, Lin X, Maki RA, Mignot E. (2001) Identification and functional analysis of mutations in the hypocretin (orexin) genes of narcoleptic canines. Genome Res 11(4):531-539. [pubmed/11282968]

Lin L, Faraco J, Li R, Kadotani H, Rogers W, et al. (1999) The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (Orexin) receptor 2 gene. Cell 98:365-376. [pubmed/10458611]