Danger mouse: deleting a gene transforms timid rodents into daredevils.

By removing one gene from a mouse's standard repertoire, scientists have turned a timid animal into an intrepid one.

Gleb Shumyatsky of Rutgers University in Piscataway, N.J., and his colleagues study the genetics that affect how animals remember scary stimuli and how they respond to fright. "Fear is definitely important when you think about the survival of an organism," Shumyatsky says. "If you make a single mistake, you can be eaten or killed."

The researchers found in 2002 that a protein called stathmin is especially abundant in the amygdala, a brain structure that processes fear and various other emotions.

To test whether the protein plays a role in controlling fear, Shumyatsky's team bred a group of mice that lack the gene that directs stathmin production. The researchers then examined these rodents' responses to stimuli designed to inspire one of two types of fear: innate fear, such as that of predators or heights, and learned fear, such as that of a sound that warns of coming pain.

When normal mice are released into a new cage, they skulk near the edges. A hardwired fear of possible predators seems to keep the animals from immediately exploring their environment. Shumyatsky and his colleagues found that mice missing stathmin strolled into the middle of new cages sooner than normal mice did. In another experiment, stath min-free mice spent more time than normal mice did on platforms set up 50 centimeters above the floor.

To investigate the rodents' learned-fear responses, Shumyatsky and his team taught groups of mice to expect a mild shock after hearing a loud tone. Normal mice froze in place for several seconds whenever they heard the tone, even if the shock didn't come. Although stathmin-free mice also struck a pose at the sound of the tone, they held it only 60 percent as long as the normal mice did.

Mice missing stathmin appeared normal in other tests of memory, hearing, and pain sensation. They also seemed to retain some fear, notes Shumyatsky. "They weren't stupid--if you wanted to catch them, they ran away," he says.

However, he and his colleagues conclude in the Nov. 18 Cell that removing the gene for stathmin seemed to blunt both innate and learned-fear responses. The results suggest a genetic explanation for why some people are daredevils while others are racked by phobias, Shumyatsky proposes.

These findings may eventually open the door to new drugs for reducing anxiety in people, says fear researcher Joseph LeDoux of New York University. However, he notes, stathmin is produced in brain areas besides the amygdala. "If you were to develop a drug based solely on [stathmin], it might not just affect fear but also other behavior," he says.