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Anxious, Aggressive Mice Used to Test Human Drugs

A Pet-1 "knockout" mouse (left) stalks a non-modified mouse in an experiment.
A Pet-1 "knockout" mouse (left) stalks a non-modified mouse in an experiment.

For many years, scientists have used animals to study diseases like cancer and diabetes. But it's been harder to find good animal models for the psychiatric problems that humans experience, says NPR's Jon Hamilton. Now, researchers say they have used genetic engineering to create a mouse that is abnormally anxious and aggressive, and that could help explain why some people are prone to anxiety or panic attacks. Hamilton reviews the research, reported in the journal Neuron.

People with low levels of a brain transmitter called serotonin often suffer from problems with aggression and anxiety. To replicate the problems in a test animal, researchers at Cleveland's Case Western Reserve University created lab mice that lack a gene needed to maintain normal serotonin levels. The genetically altered mice are called "knockout mice" because they've had a gene literally knocked out.

The altered mice were checked for an increase in aggressiveness, says researcher Evan Deneris: "We place a mouse in its home cage for a few weeks so the mouse establishes that cage as its home territory. And then after a few weeks we introduce an intruder mouse, another male mouse." While normal male mice generally show curiosity before trying to chase an intruder out of their territory, Deneris says the knockout mice "would attack the intruder much more quickly and much more vigorously … In many cases they would just see the intruder in the cage and go after it."

That, says Hamilton, "was the easy test. Measuring anxiety in mice is a bit trickier." For that, he says, scientists use a T-shaped platform several feet off the ground, in which one arm was protected by walls to give the mice a sense of safety, and the other arm is an exposed plank with nowhere to hide. Normal mice eventually explore both arms of the platform, Deneris says. The knockout mice "spent all of their time in the protected arm and would never venture into the unprotected areas."

Such mouse models have become essential in the development of drugs such as Valium or Paxil, says Michael Davis, a psychiatric researcher at Emory University. He says the genetically engineered mice also may help scientists figure out why some people are prone to excessive anxiety or aggression: Because mice and humans are remarkably similar when it comes to brain transmitters like serotonin, it's likely that some of the same genes are responsible for regulating the brain transmitters in both species. And, he says, scientists are even finding ways to create animals that exhibit aspects of complex psychiatric problems, such as depression and schizophrenia.

However, says Davis, scientists need to be cautious when using animal models created through genetic engineering: "It's conceivable that by knocking out specific genes, you're going to create mice that may have interesting properties, but will never be duplicated in nature."

Copyright 2022 NPR. To see more, visit https://www.npr.org.

Jon Hamilton is a correspondent for NPR's Science Desk. Currently he focuses on neuroscience and health risks.