A serendipitous discovery of deaf zebra fish larvae has helped narrow down the function of an elusive protein necessary for hearing and balance. The work, led by Rockefeller University’s A. James Hudspeth, suggests that hearing loss may arise from a faulty pathway that translates sound waves into electrical impulses.“These zebrafish larvae were originally pegged for another study, but then we saw that one-fourth of them failed to respond to acoustic stimuli and made erratic spiraling movements, and that suggested that they were born deaf,” says Michelle R. Gleason, who spearheaded the project. “So we took this opportunity to examine what could be responsible for this extreme hearing loss.”At first, the team didn’t detect any structural defects in the zebra fish’s inner ear. But, by comparing the genomes of normal zebra fish and the deaf ones, researchers mapped the affected DNA and then zeroed in on the precise gene, which encodes for the protein Tmie (Transmembrane iner ear). The gene had two mutations, resulting in a severely shortened protein that affected the function of the hair-like sensors, leading to hearing loss. Using powerful electron microscopy techniques (see picture), the team confirmed the deaf zebra fish had fewer and shorter kinocilia as well as a reduced number of stereocillia. But the researchers also found that the tips of the stereocilia were much thinner than normal stereocilia and lacked a tethering protein that connects one stereocilium to the next. "The findings, says Gleason, suggest that Tmie plays a bigger role in the transmission of sound than previously thought. At the ultra-structural level, we specifically show that these mutant defects map to a very specific cog in the transduction machinery. And that’s exciting because we now have a clearer target for therapy."PHOTO : D.R. Rockefeller University.Electron micrographs of two hair cell bundles in the zebra fish ear show the difference between those born with (left) and without (right) the protein Tmie.