Obsessive grooming
Is there something to it?

 Info taken from the Howard Hughes Medical Institute's web page: 
http://www.hhmi.org/news/capecchi.html          John

Mice Point to Genetic Basis for Obsessive Grooming

January 3, 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 3, 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.

"We observed that these mice appeared to keep on grooming and
biting themselves, removing their hair and finally creating skin
lesions," said Capecchi. "We theorized that the mice might have a
central nervous system defect rather than a peripheral nervous
system defect, so Joy Greer began to videotape their behavior and
analyze 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
behavior 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 behavior.

To begin to understand how Hoxb8 might control grooming behavior,
Greer and Capecchi first analyzed where the gene was expressed in
the brains of adult mice. "We found two important aspects of the
expression pattern for Hoxb8," said Capecchi. "One is that the gene
is expressed in brain regions that have become known as the 'OCD
circuit.' In clinical MRI studies of patients with
obsessive-compulsive disorder, this circuit has been shown to
function abnormally. We also found that the gene is expressed in
regions of the central nervous system known to be involved in
grooming behavior in mice per se.

"So, we believe that this gene may be involved both in terms of the
grooming behavior itself, as well as the control of the behavior,"
said Capecchi.

Capecchi speculates that the Hox genes may have multiple roles.
"These genes are important for initially governing development of
the mammalian body plan, but we postulate that they are also later
usurped for additional functions in the adult," said Capecchi. "And
we would not be surprised if they have many functions in the
nervous system, because an early evolutionary role of Hox genes is
in neural development. These functions could easily have been
adapted for neural control in the adult," he said. Capecchi also
emphasized that the abnormal grooming in the knockout mice could
prove a useful model of human obsessive-compulsive disorders.

"In particular, we believe that the Hoxb8 gene could be implicated
in the disorder trichotillomania, in which affected individuals
engage in abnormal pulling out of their hair," said Capecchi. "We
are currently collecting DNA samples from such patients to
determine whether they might have mutations in the Hoxb8 gene."
Capecchi said that his laboratory will also explore in greater
detail whether the absence of Hoxb8 causes initial abnormal
development of the relevant brain circuitry, or whether the
circuitry develops normally, but requires the gene for its proper
function in the adult animal.