Curing obsessive-compulsive mice with bone marrow transplants

Mice are also susceptible to obsessive-compulsive disorder, resulting in constant grooming that leaves them hairless and sore. Now some obsessive-compulsive mice were treated by replacing their bone marrow, demonstrating the first cause-and-effect link between the immune system and mental illness.

This pathological grooming is the mouse equivalent of the human condition of hair-pulling, known as trichotillomania. One of the most common obsessive-compulsive behaviors, it effects about 2% of the human population. University of Utah professor and Nobel prize-winner Mario Capecchi recently turned his attention to the condition, hoping to zero in on the biological component of the mental disorder.

He discovered that a mutant version of the Hoxb8 gene causes defective microglia to form in the bone marrow of mice. The microglia cells are immune system cells that travel from the bone marrow to the brain and spinal cord and are a key part of defending these areas from diseases. So Capecchi and his research partner, geneticist Shau-Kwaun Chen, transplanted bone marrow with healthy Hoxb8 genes into ten mice afflicted with the hair-pulling condition.

It took months, but the effects were obvious and enormous. All of the mice displayed far more normal grooming habits; four of the mice were completely cured, while the other six healed a lot of their wounds and regrew substantial portions of their hair. The team also tried all the other possible combinations - normal mice given mutant marrow started showing obsessive-compulsive data, normal mice given normal marrow showed no change, and mutant mice given mutant marrow exhibited extreme self-mutilation and sometimes died from their self-inflicted wounds.

Previous studies have managed to link the immune system with mental illness, but this is the first time a clear cause-and-effect link has been demonstrated in which a problem in the immune system directly affects the proper functioning of the mind. Still, while Capecchi and his colleagues think similar treatments work for humans, they don't expect to see bone marrow transplants become a common way to treat psychiatric disorders. They are among the most painful types of medical procedures and are typically only used to help treat life-threatening illnesses.

Even so, as Capecchi puts it, the basic finding from this research is astounding:

"A lot of people are going to find it amazing. That's the surprise: bone marrow can correct a behavioral defect."

[University of Utah]