The first evidence for a possible treatment for Fragile X syndrome, one of the leading inherited causes of mental retardation, has emerged from experiments with a mutant fruit fly that exhibits characteristics of the disorder. The disorder affects one in 6000 births and also causes accompanying sleep disorders, attention deficit disorder, hyperactivity, aggression, and autistic behavior.

Researchers Sean M.J. McBride from Albert Einstein College of Medicine, Thomas A. Jongens from University of Pennsylvania School of Medicine, and their colleagues studied a mutant strain of the fruit fly Drosophila that lacks the fly version of the same gene that is mutated in humans with Fragile X syndrome. The gene, FMRP, codes for a protein that binds specific messenger RNAs--carriers of genetic information in the cell--and enables them to function properly.

The mutant flies lack the ability of normal flies to adjust courtship behavior that is dependent on learning and memory. In such conditioned courtship, a male fly learns to modify his courtship behavior--including following the female, vibrating a wing, tapping the female, and attempting to copulate--according to the response of the female.

Studies of a mouse lacking the Fragile X gene had revealed that it showed increased activity of the metabotropic glutamate receptor (mGluR) on the surface of neurons. This heightened receptor activity compromises the ability of the neurons to function properly in learning and memory. Such receptors are the receiving molecules for chemical messengers called neurotransmitters, launched from one neuron to another to trigger nerve impulses in the receiving neuron.

Reasoning that mGluR hyperactivity might underlie many of the pathologies of Fragile X syndrome, McBride and his colleagues tested whether drugs that blocked the receptor's activity might restore normal function in the mutant fly. Among these drugs was lithium, which is known to affect glutamate recept
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Contact: Heidi Hardman
hhardman@cell.com
1-617-397-2879
Cell Press
2-Mar-2005

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