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A screening strategy using zebrafish targets genes that protect against hearing loss
Date:2/29/2008

ement of fluid (triggered by sound vibrations in the inner ear or changes in water pressure in the fishs environment) causes the stereocilia to tilt to one side, generating an electrical impulse that travels to the brain.

The researchers first set out to identify genes that may be involved in how hair cells respond to ototoxic medicines. Using a chemical that causes random mutations in zebrafish, the researchers bred various fish families, with each family exhibiting a different set of mutations. The researchers then exposed five-day-old larval offspring to the drug neomycin, a type of antibiotic that damages these hair cells as well as those in the human inner ear. The larvae were then stained to determine if the hair cells were still intact. Fish that were resistant to damage were quickly identified as were those that were especially vulnerable.

Using genetic techniques, the group then examined the larvaes DNA, searching for segments that were closely tied to the desired property. In doing so, they zoomed in on five mutationseach located on different genesthat, when inherited from each parent, protected against hair cell damage. Further examination revealed that one of the identified genes corresponds to a gene that is also found in other vertebrates, including humans. Another five mutations were identified that offer protection under more complex genetic conditions.

Next, the team investigated whether they could identify chemical compounds that protect hair cells against ototoxic medicines. Using the same screening techniqueexposing five-day-old zebrafish larvae to neomycin and later applying special stains to the hair cellsthe researchers screened more than 10,000 compounds and narrowed them down to two similar chemicals that provide robust protection of hair cells against the neomycin. One of the compounds was later found to protect hair cells from a mouses inner ear against the drug, indicating that the same compound may be protecti
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Contact: Mary Kohut
Press@plos.org
415-568-3457
Public Library of Science
Source:Eurekalert

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