Friday May 28 2010
Mice that lacked the Hoxb8 gene did not groom so excessively
“Bone marrow transplants cure mental illness – in mice”, reports The Guardian. The newspaper says “scientists in the US claim to have used a bone marrow transplant to cure mental illness in a study that could have profound implications for patients with psychiatric problems”.
The research involved genetically engineered mice that were lacking a gene called Hoxb8. These mice groom themselves so excessively that they remove patches of fur and develop sores. This condition is similar to a human condition called trichotillomania.
The researchers found that a type of immune system cell called microglia could be responsible for the mouse behaviour. These cells develop in the bone marrow and migrate to the brain. When the Hoxb8 mutant mice were given bone marrow from normal mice, the excessive grooming lessened and in some cased stopped completely.
These findings are of particular interest as they suggest an unexpected link between behaviour and a type of immune system cell. However, this does not mean that bone marrow transplants can cure mental illness in humans. Further research is needed to determine whether these cells play a role in humans who have trichotillomania.
Where did the story come from?
The study was carried out by researchers from the University of Utah. One of the study authors was funded by the Howard Hughes Medical Institute. The study was published in the peer-reviewed scientific journal Cell.
The Guardian provides a good account of this research, and the headline reports clearly and early on that the study is in mice.
What kind of research was this?
This research was in genetically modified mice that lacked the Hoxb8 gene. These mice groom themselves so much that they remove their fur and cause skin wounds in some areas. The reason behind this behaviour is unclear, but the researchers say it is very similar to that seen in the human condition trichotillomania, a type of obsessive-compulsive disorder where people compulsively pull out their hair. Here, the researchers were looking for a biological explanation for the mice’s behaviour.
This type of animal research is used to further understand the biological basis of human disease. Improved understanding of which cells are involved in the development of a disease may eventually help treatment for human conditions, but this process usually takes considerable time. Because of the differences between species, developing exact animal models of human diseases can be difficult. For this reason, findings in animal disease models ideally need to be confirmed in humans.
What did the research involve?
In this study, the researchers used genetically engineered mice that lacked the Hoxb8 gene. These mice display excessive grooming of themselves and their cage mates, and they have an altered perception of noxious chemicals and heat. The study aimed to determine which cells are involved in the development of these symptoms.
Expecting that the brain would be involved, the researchers began by looking at the brains of normal mice to identify the cells in which the Hoxb8 gene was active. They found that in the brains of normal mice the Hoxb8 gene was active in immune system cells called microglia. At least some of the body’s microglia develop in the bone marrow and then migrate to the brain. It was within these bone marrow-derived microglia cells that the Hoxb8 gene appeared to be active. To test the effects of the absence of Hoxb8 on microglia in the brain, the researchers compared the number of these cells in the brains of normal mice and in mice lacking Hoxb8.
To further investigate whether defective microglia cause the excessive grooming in the mice without Hoxb8, the mice were given bone marrow transplants from either normal mice or other Hoxb8-lacking mice. The theory was that a bone marrow transplant from normal mice would allow mice lacking in Hoxb8 to develop normal immune cells with active Hoxb8. If these cells were involved in this behaviour, the transplant might counteract the excessive grooming.
What were the basic results?
The researchers found that in the brains of normal mice, the only cells where the Hoxb8 gene was active were immune system cells called microglia. Adult mice that lacked Hoxb8 had fewer microglia in their brains than normal mice.
When Hoxb8 mutant mice were given a bone marrow transplant with normal bone marrow cells, the amount of excessive grooming and hair removal lessened. Some mice fully recovered. The Hoxb8 mutant mice’s noxious chemical and temperature-sensing abnormalities were not corrected by the transplant. Mice that lacked Hoxb8 and received a transplant of bone marrow cells from other mice lacking Hoxb8 did not stop their excessive grooming and hair removal.
The researchers found that if they genetically engineered mice to be missing the Hoxb8 gene in their bone marrow only, they developed the excessive grooming behaviour but not the noxious chemical and temperature-sensing abnormalities. However, if they genetically engineered mice to lack the Hoxb8 gene in their spinal cords only, the mice developed the noxious chemical and temperature-sensing abnormalities but not the excessive grooming behaviour.
How did the researchers interpret the results?
The researchers conclude that the compulsive behavioural disorder seen in mice lacking the Hoxb8 gene is associated with microglia – a type of immune cell located in the brain. This directly links mouse behaviour with the function of immune cells developed from bone marrow.
This type of animal research is used to further understand the biological basis of human disease. Improved understanding of which cells play a role in the development of a disease may eventually help treatment for human conditions, but this may well take a long time.
This research may give clues as to what type of cells may be involved in trichotillomania in humans, and is likely to spur on further research into the link between the immune system and this condition. Until this research has been completed, it will not be clear whether drugs targeting microglia might be a new way of treating this condition. As such, these findings do not have any immediate implications for treating trichotillomania.
The study does not suggest that bone marrow transplants can cure mental illness. Bone marrow transplant was simply one of the techniques used to study which cells were involved in the mice’s trichotillomania-like condition. The findings are of particular interest because a link between immune system cells and these behavioural symptoms was unexpected.