January 4, 2002 -- A gene involved in setting up the mammalian body plan also appears to control grooming behavior 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 behavioral regulators in the adult brain. Studies of the gene family could yield important insights into the genetic basis of compulsive behavior in humans.
Howard Hughes Medical Institute investigator Mario R. Capecchi and colleague Joy M. Greer, both at the University of Utah School of Medicine, reported their findings in an article published in the January 4, 2002, issue of the journal Neuron.
Greer and 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 behavioral abnormality.
Greer and Capecchi discovered that one of the approaches used in producing these knockout mice not only eliminated Hoxb8 but also interfered with neighboring 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 behavior.