Hox genes and obsessive-compulsive disorder
Some days Hox genes seem dull and psychiatric disorders seem intractably complex. And then you stumble across something like this:
Mice with mutations in the Hoxb8 gene groom themselves at about twice the frequency of wild-type mice, resulting in hair loss and open skin lesions (Greer and Capecchi, 2002). The Hoxb8 mutant mouse has been proposed as a model for a human behavioral disorder, trichotillomania (compulsive hair pulling), which may be related to obsessive-compulsive disorder (OCD; Chamberlain et al., 2006). Reporting in this issue, Chen et al., 2010 now investigate the cellular basis of the overgrooming behavior in Hoxb8 mutant mice. Reasoning that lack of Hoxb8 expression in the brain should play an important role in the behavioral phenotype, the authors ask what cell types in the brain normally express Hoxb8. They find that within the mouse brain the only Hoxb8-expressing cells are microglia that originate in bone marrow and migrate into the brain. To test whether bone marrow-derived microglia lacking Hoxb8 are responsible for compulsive grooming behavior, the authors carry out bone marrow transplants. Strikingly, transplant of wild-type bone marrow into Hoxb8 mutants restored normal, noncompulsive grooming behavior within a time frame consistent with the migration of new microglia into the brain. These findings provide important new evidence that abnormalities of the immune system can produce compulsive behavior and strengthen the case that microglia play an important role in modulation of nervous system function.
Amazing what you can cure with a bone marrow transplant…
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