Mignot and Canine Narcolepsy

At the Stanford research facility, Dr. Emmanuel Mignot worked with Dr. William C Dement, who was the first person to breed narcoleptic dogs in 1973, after he was gifted a batch of narcoleptic Doberman puppies to study a few years earlier. Since Dement found that canine narcolepsy was inherited directly from the parents and was an autosomal recessive trait (both parents needed to pass on a mutated gene for the offspring to develop the disorder), Mignot knew that he was looking for a single gene. His aim was to identify and isolate this gene, and by doing so, learn more about the genetics of human narcolepsy. At this point (about twenty years ago) only a few human diseases had been tracked back to their genes using a now outdated process known as 'positional cloning', and it took more than a decade for Mignot to locate the gene.

Finally, after isolating a big portion of DNA on chromosome 12, in 1999 Mignot pinpointed a gene that was implicated in the production of a receptor on the surface of nerve cells called the Hypocretin receptor 2. The mutation of this gene, which facilitates the transmission of messages carried by hypocretin 2, a peptide hormone in the brain (neuropeptide), was clearly responsible for canine narcolepsy.

These images show the onset and progression of a cataplectic attack in a Doberman. After spotting a treat, the dog gets excited and begins to enthusiastically eat. This emotion triggers a cataplectic attack, which involves the sudden and total relaxation of the dog's postural muscles (or muscle paralysis) for a few seconds.

Watch a video (avi format, best viewed with Windows Media Player) of Dr. Mignot talking viewers through a cataplectic attack experienced by two of the narcoleptic Dobermans he bred. (This video is courtesy the Center of Narcolepsy at the Stanford School of Medicine.)

Watch a video (avi format, best viewed with Windows Media Player) of Dr. Mignot explaining the cataplectic attack that a daschund experiences after playing with him and getting excited. (This video is courtesy the Center of Narcolepsy at the Stanford School of Medicine.)

To learn more about what Hypocretin is and how it affects the brain in narcoleptic patients browse to our page on The Hypocretin Model in Humans.