Genes for obsessive grooming? (research)

Both of these Articles are summaries of the original Research Article.
Don't know which Medical Journal the original article was published in.

(Btw, when they first planned and started these studies, TTM was
probably still listed within the OCD spectrum.)
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The first Article is taken from the Howard Hughes Medical Institute's
web page: http://www.hhmi.org/news/capecchi.html  

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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. 
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Gene for TTM? 
AOL story on Excessive Grooming/OCD 

This story was taken today from AOL Health News

Scientists Find Genes for Obsessive Grooming By Maggie Fox 
Reuters 

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WASHINGTON (Jan. 2) - 

Think your teenage daughter spends far too long in the bathroom? 

It might just be due to her genes, and her primping may actually be an
important survival behavior, scientists said on Wednesday. 

They said they had found a group of genes that, when disrupted, caused
mice to groom themselves to the point of baldness. Mario Capecchi of the
University of Utah School of Medicine, who helped lead the study, said
people have the same group of genes and they may also be involved in
grooming behavior. If so, further studies could help explain
obsessive-compulsive disorder (OCD). 

"People with obsessive-compulsive disorder can spend an enormous amount
of time washing their hands, to the point where they get bleeding
sometimes," Capecchi said in a telephone interview. That is only one
manifestation of OCD, which can cause a range of behaviors. But it is
similar enough to what the mice do to make Capecchi believe there is a
link. 

"In terms of genes, we are 99 percent the same" as mice, Capecchi, a
geneticist, said. "Now what we have to do is go to populations that have
obsessive-compulsive disorder and then start looking at their DNA to see
if this particular gene is affected." 

Studies with twins show that OCD has a genetic basis -- identical twins
are more likely to have OCD if their twin has it, Capecchi said. 

His team had been examining a group of genes called Hoxb genes,
specifically one called Hoxb8. They are very important in development
and are very similar in all mammals. 

"It is a very basic gene," Capecchi said. "It is important during the
early part of your life. It is involved in making parts of your brain,
all the bones in your body, organs in particular places." 

So how could it have a role in behavior? "What we are finding is that
genes normally don't have a single role. They have multiple roles,"
Capecchi said. "This whole complex may be involved extensively in the
adult." 

It would make sense that mammals would share a gene for grooming,
Capecchi said. Even fruit flies groom themselves. "We often neglect it
but terms of survival grooming is actually important," Capecchi said. 

For example, he said, when people invented cotton clothing, they could
wash their clothes and their bodies more often, getting rid of fleas,
germs and parasites. Just about the time Europe started importing cotton
from Egypt, life expectancy went up, he said. "That gives you an
indication of the importance of grooming," Capecchi said. 

So he said parents should not complain when teenagers spend hours in the
bathroom. "As long as they are grooming, that is probably OK," he said. 

Capecchi and colleagues found the role of the hoxb8 gene by creating
mice that lacked a normal version of the gene. The mice ended up with
bald patches. 

But, the researchers reported in the Jan. 2 issue of the journal Neuron,
they were not sure why the mice were bald -- were they grooming too
much, did they have itchy skin, or was something else wrong? So they
videotaped their mice. Not only did the mutants groom themselves bald,
but they also licked and nibbled their normal cage-mates for hours. 

"They have fairly normal grooming behavior -- they just spend enormous
amounts of time doing it," Capecchi said. 

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