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Gene Mutation Found For Common Form Of Mental Retardation

Defect Supports New View Of Nerve Signaling In Learning And Memory

BOSTON-August 26, 1998--A gene mutation responsible for a form of mental retardation affecting one in 600 males has been located on the X chromosome, researchers from Beth Israel Deaconess Medical Center, Harvard Medical School, and other institutions report in the September Nature Genetics.

Genes for nonsyndromic mental retardation (MRX) have been prized quarry for neurobiologists because unlike other inherited forms of retardation, which involve several organs, MRX appears to affect only the brain. MRX genes therefore give dramatic insight into brain development. The discovery that this defect causes severe cognitive problems, and occurs in a gene that normally regulates neuron shape, gives a new look at how neurons interact in learning and memory.

Traditionally, mature neurons were thought to convey messages by changing their chemical and electrical properties, not by boosting or blocking signals from their neighbors by changing shape. "Previously, people had only static pictures, electron micrographs and the like," says co-author Christopher A. Walsh, a Harvard Medical School researcher at Beth Israel Deaconess.

Using more advanced techniques, researchers have begun to see that electrical transmission is accompanied by movement at the tiny spines located along the neuron's receiving arms, or dendrites. The spines, which accept input from the axons of other nerve cells, appear to contract and expand, increasing or decreasing the ease with which the dendrites conduct electrical impulses.

"So a neuron can sort of tune in one synapse and tune out another by changing the shape of the spine," says Walsh who, with HMS colleagues Kristina Allen and Joseph Gleeson, instructors in neurology at Beth Israel Deaconess and Children's Hospital, respectively, discovered the new X-linked mutant.

As it turns out, the defect, which
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Contact: Bill Schaller
schaller@hms.harvard.edu
(617) 432-0441
Harvard Medical School
1-Sep-1998


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