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Key gene identified for development of inner-ear structure required for balance

Bar Harbor, Maine--Ears do more than hear; they also control balance and our perception of gravity and motion. An international team of scientists including David E. Bergstrom and John C. Schimenti, at The Jackson Laboratory in Bar Harbor; and Rainer Paffenholz and Gabriele Stumm at Ingenium Pharmaceuticals AG in Martinsried, Germany, identified for the first time a protein whose enzymatic function is indispensable for development of this balance system.

The scientists had known that mice with the head tilt mutation known as het hear perfectly well, but carry their head at an angle and lack coordination. Mice and humans sense motion in the same way. When our heads move, a cluster of crystalline structures known as otoconia in the inner ear moves somewhat independently. This shearing motion stimulates underlying nerve endings to create the sensation of motion.

The scientists found the head-tilt mice have no otoconia, but otherwise exhibit perfect inner ear formation. "Because animals use otoconia to sense their orientation in space and to monitor posture and movements, the behavior and motor coordination deficits of [the mice] can be conclusively explained by the lack of otoconia," the researchers note in the paper.

Prior research had located the head-tilt mutation to a large region on Chromosome 17. "We had access to five strains of mice with the defect," Bergstrom explains, "and we used these mice in breeding experiments to zero in on the chromosomal location of, and eventually identify, the underlying mutant gene, Nox3." While the exact process of otoconia formation has yet to be defined, this identifies for the first time a protein with a clear enzymatic function as indispensable for otoconia formation, the scientists note.

The mouse gene corresponds to the human gene NOX3. In both mouse and human, the gene affects production of the protein NADPH oxidase 3. Aging, some medications, infections and injury can damage otoconia, resul
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Contact: Heather Cosel
coselpie@cshl.org
Cold Spring Harbor Laboratory
8-Mar-2004


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