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Understanding Fragile X syndrome with the blink of an eye

While researchers have long known the genetic defect underlying Fragile X syndrome, they are still tracing how that defect creates the complex mix of mental retardation, hyperactive behavior, attention deficits, and other problems in the disorder. Fragile X is particularly important because it is the most common single-gene cause of mental retardation--affecting about 1 in 4000 males and 1 in 8000 females in the U.S.

In an article in the August 4, 2005, issue of Neuron, researchers led by Chris De Zeeuw of Erasmus University Rotterdam report that they have pinpointed a specific cause of defects in motor learning in Fragile X patients. Their work represents the first investigation of the role of abnormalities in the brain's cerebellum in Fragile X syndrome.

Fragile X syndrome is caused by a defect in the Fragile X mental retardation 1 (Fmr1) gene, which in turns produces a nonfunctioning protein, FMRP. In their studies, De Zeeuw and colleagues studied the behavioral effects on motor learning and the effects on neurons in the cerebellum of knocking out this gene.

They found that mice lacking the gene showed deficits in a particular motor learning task known to be largely controlled by the cerebellum. In this "eyeblink conditioning" task, the mice were taught to associate a stimulus such as a tone with a puff of air on their eye, and the blink response was measured as an indication of how well the animals could learn the task. The researchers found that mice completely lacking the Fmr1 gene showed deficits in the motor learning task. But most importantly, the researchers also found that mice lacking the Fmr1 gene only in specific neurons, called Purkinje cells, in the cerebellum showed the deficit.

Detailed electrophysiological studies of Purkinje cells in such mutant mice revealed that the cells showed an enhanced weakening of their signaling connections--called long-term depression. The researchers also found that the Purkinje c
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
3-Aug-2005


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