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Of Mice and Mayhem

The Fierce Tempers of Mutant Rodents Born With Their Brains Awash in the Chemical Serotonin May Provide a Clue to Violent Behavior Among Humans


Given the Dutch findings, then, it was logical for the sore-fingered French researchers to want to know if their mutant mice also lacked the MAO enzyme. That's where Shih, a world expert on that family of enzymes, came in. Not long after she agreed to test the Tg8 mice for the enzyme, a shipment of the creatures arrived from France (having spent weeks in quarantine at Los Angeles International Airport).

It took Shih and her co-workers several months of painstaking lab work to establish that the male mice were indeed lacking the gene for the MAO-A enzyme--just like the affected Dutchmen. "When this gene is missing, the animals are very aggressive and hyperactive," Shih says.

Her Tg8 study, says Randy Nelson, a behavioral psychologist at Johns Hopkins University, was "one of the first to show a biological mechanism for aggressive behavior in an animal." Follow-up studies published this spring in the journal Neuron suggest that the neurotransmitter defect actually affects the structure of the Tg8's brain, most likely by skewing growth and development in fetal and newborn mice.

Nelson says it's no surprise that genes affect temperament. "Anybody who knows the difference between a pit bull and a Labrador retriever knows that aggressive behavior has a genetic basis," he says.

Some researchers expect that the biochemical analysis of behavior will pay off. Dr. Frederick Moeller, a psychiatrist at the University of Texas in Houston, hopes that the missing-enzyme research leads to new drugs for treating criminals and other violent people who simply can't control their aggression. "I treat individuals who . . . can't keep from assaulting hospital staff even long enough to get out of the hospital," he says.

"The goal isn't to control everybody and make them less aggressive," he says. "The goal is to work with real people who have a real problem with aggression."

For her part, Shih is a little dismayed to find herself in the middle of such a hot controversy. "I like to avoid the political issues," the biochemist says.

Even though she is no sociologist, Shih believes that she can make a contribution to understanding human behavior by studying the Tg8's biology.

That possibility is apparent to her whenever she returns the mice to their cages in the locked, windowless animal room across the hall from her office. Normal mice fare perfectly well living four to a cage. But the Tg8 males are held in solitary confinement, too hostile for mouse society.

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