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November '06
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Man's Best Model

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FEATURES: Man's Best Model

PAGE 2 OF 6

This time the interlude lasts just a moment. After a rousing pat on the head, Bear resumes his meal, apparently none the worse. “They become overstimulated by food, or play, or sex,” sighs Mignot. “You can imagine what it was like trying to breed a colony of narcoleptic dogs.”

Well, no, actually. Still, while every animal model of human behavior has its own special challenges, they remain essential to investigators. Molecular biologists depend on our evolutionary relatives to illumine the biochemical circuitry that drives us.

“Neurology has been revolutionized by the existence of animal models,” says neurobiologist Eric R. Kandel, a Nobel laureate and HHMI investigator at Columbia University. “The brain of a mouse is a prototypic mammalian brain. Evolution has been quite conservative across mammalian species.”

An Underused Model
Increasingly, scientists see in animals the underpinnings of behavioral responses once thought to be uniquely human: depression, happiness, even lust. Whether the researchers' experiments lead to new therapies, the very fact that many of these behaviors can be modeled in animals comes as something of a shock.

A depressed mouse? An insomniac fruit fly? C'mon.

Yet these beasts do exist—scientists have had only to look for them or, more recently, to create them. In the early 1970s, at an American Medical Association conference in San Francisco, sleep researcher William C. Dement of Stanford University School of Medicine described to his audience the bizarre symptoms of narcolepsy: waves of unstoppable drowsiness, fragmented sleep patterns, episodes of quasi-paralysis at times of strong emotion. An estimated 150,000 people have the disease, he noted, and for them daily life is a perilous obstacle course.

After the talk, a doctor visiting from Canada told Dement that he had seen this syndrome all too recently—in his dog. Far from finding a potential connection laughable, Dement scouted among local breeders for similarly affected animals, ultimately establishing a colony of narcoleptic Doberman pinschers and Labrador retrievers at the university. As it turned out, he could not have picked a better way to study the disease.

Because they are highly inbred and often geographically isolated, dogs harbor more than 300 genetic diseases, researchers now know—more than any other species besides humans. At least half of these diseases are believed to be analogous to specific human disorders. Seventeen breeds, including dachshunds and poodles, are known to develop narcolepsy.

“The dog genome is very similar to the human genome,” says Mignot. “They really have not been used enough as models.”

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HHMI INVESTIGATOR

Emmanuel Mignot
Emmanuel Mignot
 
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