C110 - Canine Narcolepsy

Sleep is vital behavior of an unknown function that consumes one-third of any given human life. Narcolepsy is a debilitating neurological disease characterized by abnormally fragmented night-time ‘REM’ sleep, constant day time sleepiness, and irresistible ‘sleep attacks’ that occur even when the sufferer is walking and talking. It is the only known neurological disease that specifically affects the generation and organization of sleep. In 1999, a ground-breaking study revealed the gene responsible for this disease in narcoleptic Doberman Pinschers. Further studies have demonstrated a close similarity between human and canine narcolepsy. Researchers identified that canine narcolepsy is caused by a mutation in the hypocretin receptor 2 gene (Hcrtr2). Cells' bodies that contain hypocretins (a novel neuropeptide that possesses excitatory effects) are found in the hypothalamus, an area of the brain responsible for various regulatory functions in the body. These neurons project into many other areas of the brain, like the brainstem (where the pons are located), responsible for REM sleep. It is hypothesized that hypocretins may play a role in modulating neurons involved in REM sleep, helping in the interaction between two chemical systems in the brain, the aminergic and the cholinergic. Researchers also hypothesized that when the Hcrtr2 is stimulated, administration of hypocretins promotes wakefulness and represses REM sleep in normal, but not narcoleptic animals.

Canine narcolepsy in Doberman Pinschers and Labrador Retrievers shows an autosomal recessive mode of inheritance; therefore two copies of the defective gene (one inherited from each parent) have to be present for a dog to be affected by the disease. Dogs with one copy of the defective gene and one copy of the normal gene - called carriers - show no symptoms but can pass the defective gene onto their offspring. When two apparently healthy carriers are crossed, 25% (on average) of their offspring will be affected by the disease with a further 50% being carriers themselves.

Canines affected with narcolepsy typically display symptoms that are specific to the disease. Therefore, diagnosis of this disorder is usually based on clinical findings. Carriers of the gene responsible for narcolepsy display no symptoms of disease and therefore, cannot be identified by clinical observation. Recently, a DNA-based test for the detection of the gene responsible for narcolepsy in Doberman Pinschers and Labrador Retrievers became available. Since this test directly targets the narcoleptic gene, it is 100% accurate and provides breeders with definitive information on the genetic status of their animals. Breeders can use this information to detect carriers and eliminate this disease from their breeding lines.