Gene Leads to Jumpy, Grumpy Mice

The loss of a single gene in mice can affect social behavior and impair their brains' ability to filter out distractions--both characteristics of several neurological diseases in humans. The finding, reported in today's issue of Cell, could give researchers an animal model for figuring out aspects of the biochemistry underlying schizophrenia and other conditions.

Although researchers knew that the gene, called dishevelled 1, is expressed in the brain, its specific role has been a mystery. To see if they could deduce the role the gene plays in mice, a team of scientists, including Anthony Wynshaw-Boris and Nardos Lijam of the National Human Genome Research Institute in Bethesda, Maryland, and Richard Paylor of the National Institute of Mental Health (NIMH), also in Bethesda, created a strain of mice that had no copies of the gene.

The mice had no apparent physical abnormalities, and they performed learning and motor tasks just as well as normal mice. However, says Wynshaw-Boris, they seemed to interact with each other differently. In normal mouse groups, the dominant mouse trims the whiskers and facial hair of subordinate mice, but the mutant mice, which were housed together, all had full sets of whiskers. In addition, the researchers observed that the mutant mice did not build normal nests and did not sleep huddled together as mice usually do. Instead, they spread out across their cages. That a single gene can alter such complex social behavior is surprising, says Wynshaw-Boris.

The team also tested the ability of the mutant mice to filter out distracting stimuli. A standard way to test so-called sensorimotor gating is to startle an animal or person with a loud sound. In normal animals, a soft sound milliseconds before the loud sound will subconsciously warn the brain and suppress the startle response. But the mutant mice were still quite startled, even with the warning sound. Some patients with schizophrenia, obsessive-compulsive disorder, Huntington's disease, and Tourette's syndrome exhibit a similar deficit, suggesting that the inability to filter out stimuli might play a role in those conditions.

Although the researchers caution that their work does not prove a link between the gene and such diseases, it does provide some very interesting clues, says Steve Moldin of the Genetics Research branch at NIMH. "It's potentially very exciting," he says, because the mouse model might give researchers a chance to uncover the biochemical pathways that control the specific behaviors.

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