Genetic basis for obsessive grooming

A gene involved in setting up the mammalian body plan also appears to control grooming behaviour in mice.

Researchers who knocked out a specific homeobox, or Hox, gene in mice also noted that the mice groomed themselves excessively, creating bald spots and skin wounds. The discovery suggests that the Hox genes, a large family of development-controlling genes, might also serve as behavioural regulators in the adult brain.

Two Howard Hughes Medical Institute investigators, Joy Greer and Mario Capecchi, created two different genetically altered strains of mice that lacked functional Hoxb8 genes. Like other Hox genes, Hoxb8 produces a transcription factor, a protein that controls the activity of other genes.

Other researchers who had created Hoxb8-knockout mice had observed abnormalities in the ribs and cranial nerves and noted an impaired reaching reflex in their animals. Those scientists had also reported that some of the mice engaged in self-mutilation, but they proposed that the disorder might be caused by a defect in the animals' ability to sense pain, rather than a behavioural abnormality.

Greer and Capecchi discovered that one of the approaches used in producing these knockout mice not only eliminated Hoxb8 but also interfered with neighbouring Hox genes. When Greer and Capecchi created mice in which only Hoxb8 activity was eliminated, they saw no physiological malformations in the mice, but only the abnormal grooming behaviour.

"We observed that these mice appeared to keep on grooming and biting themselves, removing their hair and finally creating skin lesions," said Capecchi. "We theorised that the mice might have a central nervous system defect rather than a peripheral nervous system defect, so Joy Greer began to videotape their behaviour and analyse it more closely." Videotaping revealed that Hoxb8 knockout mice groomed themselves more frequently and longer, and spent about twice as much time grooming as normal mice. Analysis of the videotapes also showed that the mutant mice also excessively groomed their normal cage mates.

"The grooming of cage mates was normal grooming and not a dominance behaviour called 'barbering,' in which mice remove the whiskers of other mice," said Capecchi. "Also, the cage mate grooming demonstrated that the knockout mice were not just grooming themselves because they had a skin disorder that caused itching."

The researchers also found that the mutant mice groomed more than wild-type mice when grooming was induced by misting the animals with water. And when the scientists produced Hoxb8-knockout mice that were otherwise genetically different from their initial mutant strain, those mice also showed the same abnormal grooming — further demonstrating that the Hoxb8 gene defect alone was responsible for the abnormal behaviour.