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Mice Grow More Hearing Cells After Gene Transfer

Electron micrographs show V-shaped clusters of microscopic hair-like structures on hair cell surfaces. Mice with Atoh1 (right) have more hair cells than mice without the gene transfer (left).David Woessner, John Mitchell and John V. Brigande, Oregon Health and Science University.

Researchers have used gene transfer to produce functional hair cells in the inner ears of mice. The accomplishment is an important step in developing potential strategies to treat hearing impairment.

Auditory hair cells in the inner ear are a vital part of our hearing, and their loss is a leading cause of hearing impairment. These cells turn the vibrations of sound energy into electrical signals that travel to the brain. Over the past few years, researchers have made significant progress in understanding how these cells perform this feat. They've also been able to use gene transfer to produce new hair cells and partially restore hearing in deaf adult mammals.

A team of researchers led by Dr. John V. Brigande at the Oregon Health and Science University set out to see if they could use gene transfer to produce functional sensory hair cells in mice, which would allow for a better understanding of the new cells and how they develop. The study was supported by NIH's National Institute on Deafness and Other Communication Disorders (NIDCD), along with the McKnight Endowment Fund for Neuroscience and the American Otological Society.

In the online edition of Nature on August 27, 2008, the researchers reported that they devised a method for inserting genes into the region of embryonic mice that develops into the inner ear. The process didn't appear to affect the mice's hearing. Once the scientists had accomplished this, they transferred the gene for Atoh1, which is known to be required for hair-cell formation, into the region.

The genetically altered mice had a 1.8-fold increase in inner ear hair cells. The cells appeared to connect properly to neurons. The researchers tested whether the cells could convert mechanical stimuli into electrical impulses, and found the cells to be fully functional.

“The problem with losing hair cells is that our bodies can not replace them. If they are damaged, broken, or missing, our hearing declines. Dr. Brigande's team has demonstrated a technique that will stimulate research on genetic therapies for hearing loss. It's an important step,” says Dr. Matthew Kelley, chief of the NIDCD Developmental Neuroscience Section.

The next step for the research team will be to use the technique they developed to try to treat hearing loss in mouse models of human deafness and balance disorders. Ultimately, this research may lead to therapies for treating hearing problems in people.

— by Harrison Wein, Ph.D.