Clinical geneticist Anthony Wynshaw-Boris never expected to dabble in rodent psychiatry. But he did more than dabble when he created mice lacking a key developmental gene. In September his group at the National Human Genome Research Institute in Bethesda, Maryland, announced that those mice show behavioral abnormalities similar to ones seen in human disorders such as schizophrenia, autism, and Tourette’s syndrome.
The gene in question, Dishevelled-1, is so essential to development that it is found in animals as distantly related as fruit flies, mice, and humans. When the gene is removed, or ‘knocked out,’ from fruit-fly embryos, larvae emerge with scrambled body parts. Wynshaw-Boris and his colleagues had expected equally drastic effects in mice.
But the mice appeared completely healthy—even in the anatomy of their brains, where the Dishevelled-1 gene is very active. Eventually, though, the researchers noticed something odd: all the knockout mice had whiskers, while none of the normal mice did. Since the barbering of whiskers is a common social behavior in this strain of mice, Wynshaw-Boris and his team took a closer look. Video recordings revealed that the mutant mice did not groom each other much and did not huddle in fluffy nests—in short, they did not socialize the way normal mice do.
They also flunked a test that stumps schizophrenics. Normal mice and normal humans are far less startled by a sudden loud sound if it is preceded by a soft one. But the mutant mice—like schizophrenics and other psychiatric patients—were just as startled with or without an alerting sound. In human patients, that performance is interpreted as symptomatic of an inability to filter incoming information and recognize when it’s worth attending to.
Other researchers are now looking for evidence that the Dishevelled-1 gene is indeed mutated in psychiatric patients—although what it does in the brain remains a mystery. We think Dishevelled would be a candidate gene for several human psychiatric disorders, says Wynshaw-Boris. Meanwhile, his strange mice may lead to better treatments for those disorders: they make good laboratory models for testing new drugs.
