Fragile-X-syndrome research

Jun 20 2005

The fragile-X-syndrome is the most common hereditary form of mental retardation and occurs much more often in boys than in girls.

Children with the fragile-X-syndrome have certain characteristic features, such as a long face with a large chin, protruding ears, and a high forehead. As a child, they frequently have behavior problems and are sometimes hyperactive, agitated, and clumsy. They are usually mentally handicapped, but the degree of handicap differs from person to person. The behavior problems diminish with the onset of puberty, while the mental handicap remains.

Since 1991, scientists have known which genetic alteration lies at the basis of the fragile-X-syndrome. This alteration causes the FMRP protein (Fragile X mental retardation protein, named after the syndrome) to lose its function. However, up to now, it has not been clear which bodily reactions are blocked by the loss of function of this one gene, given the fact that the FMRP controls the functioning of many other genes as well. Shedding light on this situation is one of the great challenges for researchers who want to better understand the syndrome and, consequently, the functioning and development of the brain.

Bassem Hassan's group specializes in this area of research, using fruit flies because they contain the dFMRP protein, which is analogous to the human FMRP protein. Just like humans with the fragile-X-syndrome, fruit flies in which the dFMRP gene has been knocked out display behavior problems and disturbances in the brain. It is these modified flies that the research team in Leuven is using as their model system.

Their research has led to the discovery that fruit flies that produce no dFMRP in turn produce more profilin. Profilin, a protein, regulates the dynamics of actin, which has a very important function regarding the form and structure of all types of cells, including neurons. Actin acts as a kind of scaffolding that supports the cell and gives it shape. Too much profilin disturbs the regulation of actin, giving rise to abnormal neuron sub-divisions. The researchers found this clearly in the fruit flies that produce no dFMRP.

With this research, Bassem Hassan and his group (Simon Reeve, Laura Bassetto, and Maarten Leyssen) are the first to demonstrate that dFMRP controls the regulation of the actin skeleton. In fruit flies that produce less or no dFMRP, this entire process goes awry and the neurons no longer form the correct patterns. This is probably also the case for humans, and so this research can lead to a better understanding of the fragile-X-syndrome, and also of the brain's development. Therefore, the researchers now propose to study this result, which they have obtained in fruit flies, in mice models. These mammals, of course, are a rung closer to humans on the evolution ladder.