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Mutant gene shatters nerves

If you bend a knee or an elbow, the nerves in your limbs stretch but do not break. A University of Utah study suggests why: A gene produces a springy protein that keeps nerve cells flexible. When the gene was disabled in tiny nematode worms, their nerve cells literally broke.

The discovery may provide a new explanation for spinocerebellar ataxia type 5 (SCA5) ? a disease previously tied to a human version of the gene and identified in 11 generations of U.S. President Abraham Lincoln's family, starting with his paternal grandparents. SCA5 may have afflicted Lincoln himself. The new study suggests how.

"Were Lincoln's nerves shattered? We don't know. But our study raises the possibility that they were," says biology Professor Michael Bastiani, the study's senior author and a member of the Brain Institute at the University of Utah.

The new study will be published in The Journal of Cell Biology on Jan. 29, two weeks before Lincoln's birthday on Feb. 12.

The study involved a worm gene named unc-70 that makes a protein named beta spectrin. Humans have four beta spectrin genes, and mutations in one of them was identified previously as the cause of SCA5, a neurodegenerative disease that develops between ages 10 and 68; destroys nerve cells in the part of the brain that controls movements; causes loss of coordination in walking, speaking, writing and swallowing; and puts some patients in wheelchairs.

Other researchers previously suggested the disease occurs because the mutation leaves beta spectrin unable to anchor other proteins to their proper places in nerve cells, so the cells cannot communicate normally. But the worm study suggests the true cause is nerve-cell breakage caused by defective beta spectrin, says study co-author and biology Professor Erik Jorgensen, scientific director of the Brain Institute at the University of Utah and an investigator with the Howard Hughes Medical Institute (HHMI).

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Contact: Lee Siegel
leesiegel@ucomm.utah.edu
801-581-8993
University of Utah
29-Jan-2007


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