This proposal seeks continuation of support for maintenance of an indispensable national resource--a colony of dogs which provides the only existing animal model of the human disease of narcolepsy. These animals manifest the identical pathognomonic signs found in human narcolepsy (namely, sleep onset REM periods and bouts of cataplexy) and genetically transmit this trait. Recent research investigations have identified specific neurochemical defects in the brains of affected animals that may reflect the underlying neural basis of this disease. We plan to maintain a breeding colony of 25 dogs with heritable narcolepsy for five years and a research colony of 80 narcoleptic dogs/year reared to 100 days of age. The dog breeds that will be maintained are Doberman pinschers, Labrador retrievers, and Labrador-Doberman mixtures, all of which transmit the narcoleptic trait genetically. The narcoleptic dog colony is a necessary resource for current and future projects for both Stanford and extra-Stanford investigators. It is the only colony of narcoleptic animals in the world. The research projects made possible by the existence of this colony will elucidate the neurochemical and genetic causes of narcolepsy, clarify the mechanisms of symptoms, such as excessive sleepiness and hallucinations, present in other human illnesses, and provide insights into the basic mechanisms of sleep.
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