Ancient Gene Takes Grooming in Hand

All sorts of animals groom themselves regularly, which keeps them clean and healthy. However, mice with an alteration in one of the genes that orchestrate body development lose their grip on grooming, a new study finds.

These mice bite and lick themselves so hard and so often that they end up with bald patches and open sores, according to Joy M. Greer and Mario R. Capecchi, both geneticists at the University of Utah in Salt Lake City. Moreover, the same genetically altered rodents groom cage mates just as aggressively.

The mice have a mutated version of one of the homeobox, or Hox, genes, which scientists have implicated in embryo development. The new finding offers a potential avenue for exploring the biological roots of trichotillomania, a rare condition in which people tear out their hair, as well as some of the repetitive cleaning behaviors classed as obsessive-compulsive disorder (OCD), the researchers conclude in the Jan. 3 Neuron.

“This particular Hox gene may regulate the amount of grooming performed by an animal,” Capecchi says. “So far, we see no other unusual behaviors in mice with this mutation.”

The study adds to emerging evidence that Hox genes, which are largely the same in all vertebrate species, influence biology and behavior in a surprisingly wide variety of ways, he adds. It makes sense, in his view, that at least one of these evolutionarily ancient genes influences the comparably ancient grooming practices of vertebrates.

Greer and Capecchi altered one of the two copies of the Hoxb8 gene in individual mice from an inbred line. This enabled the scientists to compare these animals with others in the line, which shared the same set of genes except for the critical Hoxb8 mutation.

As adults, genetically modified mice displayed bald patches and skin lesions on their bodies. The researchers found large amounts of hair in the rodents’ mouths and stomachs.

Videotaping for 24 hours showed that mice with Hoxb8 mutations spent twice as much time grooming themselves as the other mice did. Hoxb8 mice also doggedly groomed their cage mates.

Further evidence of a Hoxb8 influence on excessive grooming came when Greer and Capecchi found that mutant mice didn’t have any other condition that might cause such behavior. For instance, the animals were as sensitive to pain as other mice were and had no irritating skin conditions.

Laboratory analyses of the brains of the mutant mice then revealed molecular footprints of Hoxb8 activity in areas that had already been implicated in control of animal grooming and generation of human OCD symptoms, such as compulsive hand washing.

Psychiatrist James F. Leckman of Yale University School of Medicine calls the new finding about the Hoxb8 gene “very exciting.” Leckman’s group is currently investigating possible effects of other Hox genes on OCD.

The Hoxb8 mutation described by the Utah scientists may also shed light on body dysmorphic disorder, Leckman holds. In this OCD-related condition, people experience debilitating preoccupations with imagined physical defects.

Still, the Hoxb8-mutated mice behaved much as people with trichotillomania do, comments psychiatrist Lewis R. Baxter of the University of Alabama at Birmingham. Researchers need to explore whether prescription drugs that ease trichotillomania and OCD trim back grooming in Hoxb8 mice, Baxter says. These medications boost the activity of serotonin, a chemical messenger in the brain.

Greer and Capecchi are already examining whether the mutation that they identified in mice appears in people diagnosed with trichotillomania.

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