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Cellular channels vital for hearing identified
Date:7/18/2013

Boston, Mass., July 18, 2012 Ending a 30-year search by scientists, researchers at Boston Children's Hospital have identified two proteins in the inner ear that are critical for hearing, which, when damaged by genetic mutations, cause a form of delayed, progressive hearing loss. Findings were published online July 18 by the journal Neuron.

The mutations, affecting genes known as TMC1 and TMC2, were reported in 2011 by the laboratory of Jeffrey Holt, PhD, in the Department of Otolaryngology at Boston Children's. Until now, however, it wasn't clear what the genes do. In the new study, Holt and colleagues at the National Institute on Deafness and Other Communication Disorders (NIDCD) show that the proteins encoded by the genes form channels that turn mechanical sound waves into electrical signals that talk to the brain. A tiny point mutationa change in one base or "letter" in the genetic sequenceis enough to cause deafness.

Corresponding channels for each of the other senses were identified years ago, but the sensory transduction channel for both hearing and the sense of balance had remained a mystery, says Holt.

The study involved so-called Beethoven mice that carry mutations on TMC1 and become deaf by their second month of life. Each mutation has a human counterpart that causes a prominent form of genetic deafness, causing children to become completely deaf by the age of 10 to 15 years.

Studies of sensory hair cells from the cochleas of the mice, which sense sound vibrations and signal the brain, showed that the TMC1 and TMC2 proteins are necessary to get calcium into the cells. The researchers showed that when TMC1 was mutated, the calcium influx was reduced and the resulting electrical current was weaker in response to sound. "This is the smoking gun we've been looking for," says Holt.

The study also provided evidence that:

  • The TMC1 and TMC2 proteins act as backups for each other, explai
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Contact: Meghan Weber
meghan.weber@childrens.harvard.edu
617-919-3656
Boston Children's Hospital
Source:Eurekalert

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