Give a treat to a narcoleptic dog, and he's likely to pass out with excitement - an endearingly pitiful sight. However, such canines are helping scientists understand human narcolepsy and sleep control. In the April issue of Genome Research, Emmanuel Mignot and colleagues from Stanford University Medical Center shed light on the brain defects that lead to canine narcolepsy.
Previous studies suggest varying causes for narcolepsy in humans and dogs, but recent work strongly implicates the hypocretin system, a network of brain cells that releases a chemical called hypocretin/orexin. Narcolepsy correlates with deficits in hypocretin cells or in the receptors that detect hypocretin (called Hcrtr2). In the current study, Mignot and colleagues examine the Hcrtr2 gene in narcoleptic poodles, Labradors, Dachshunds, and Dobermans. The researchers describe a novel, naturally occurring mutation of the Hcrtr2 gene that leads to receptor dysfunction and correlates with narcoleptic symptoms. These findings confirm the importance of the Hcrtr2 receptor in canine narcolepsy. However, as in narcoleptic humans, many narcoleptic dogs in this study showed no mutations in the Hcrtr2 gene. In such cases, narcolepsy might be due rather to degeneration of the hypocretin system, which might be treatable by "hypocretin replacement therapy." The present findings indicate that narcoleptic dogs will continue to shed light on the causes and treatment of human narcolepsy.