Fearless Mice May Shed Light on Fearful Humans

Scientists have created a brave mouse that may eventually help scientists understand fearful people.

Gleb Shumansky of Rutgers University in Piscataway, N.J., says a typical mouse tends to hug the walls and hide in corners. But he's been working with mice that don't act this way.

"They're kind of like fearless mice," he says. "They go to open spaces. They explore freely. And really for mice it's not a good thing because some predator can come and eat them."

The mice are fearless because they have been genetically modified. They are missing a gene called stathmin.

Removing that gene reduces the fears normal mice are born with — fears of things like open spaces. It also reduces their ability to learn to fear things, such as a tone that is always followed by an electric shock.

Shumyatsky, whose study appears in the journal Cell, says the discovery of the significance of stathmin came from an unusual effort to look at about 5,000 genes in the amygdala — the area of the brain involved in fear.

When members of his team looked at the brains of normal, anxious mice, they found high levels of the protein associated with the stathmin gene.

Shumyatsky says the big question is whether stathmin plays a role in making people anxious.

"Because stathmin is in mice and in humans, and the protein is very similar in both, and the amygdala is also present in both species, I think that what we see in mice we can replicate in humans," he says.

If Shumyatsky is right, the amygdalas of people with anxiety disorders would have high levels of the stathmin protein. Experiments to find out are a ways off.

In the meantime, Shumyatsky's team has shown that brain researchers need to look beyond the usual suspects — the genes associated with neurotransmitters like serotonin and dopamine.

Dr. Thomas Insel, the director of the National Institute of Mental Health, says researchers have devoted almost all their time to perhaps 1 percent of the total number of genes active in the brain.

"What's exciting about this paper is this is coming from that other 99 percent," he says. "This is a pretty obscure gene and a fairly obscure protein. It's been known a little in the cancer literature. But this is a new player, and one that may turn out to be very important.

Until now, stathmin has been known primarily for its role in leukemia.

Insel says Shumyatsky's team succeeded by working backward. Instead of starting with a well-known gene and trying to link its protein to a certain behavior, they systematically examined all the possibilities.

"Now they've got this one, stathmin," he says. "My goodness, we had no reason to think it was even found in this area of the brain. It turns out to be heavily enriched in this part of the brain, suggesting that maybe it has some kind of a role related to fear and anxiety."

Insel says the discovery does not suggest there will be a cure for human anxiety anytime soon. But he adds, "It does suggest that maybe we have a new target for looking at the development of treatments."

Insel says even if this gene doesn't pan out, other previously ignored genes probably will. He says scientists are only beginning to discover all the genes that control the brain.



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