Gene Transfer in Mice Produces Functional Hair Cells Crucial to Hearing

An NIDCD-funded research team’s recent finding provides further evidence that it might be possible in the future to restore hearing with a genetic message that directs the inner ear to grow new hair cells.

Researchers led by John Brigande, Ph.D., an assistant professor of otolaryngology in the Oregon Hearing Research Center at the Oregon Health & Science University, recently published their findings online in the journal Nature. Working with embryonic mice, the team demonstrated that they could trigger hair cell growth by transferring a gene known as Atoh1 into the mouse inner ear.

Hair cells are tiny structures within the cochlea of the inner ear [see diagram at www.nidcd.nih.gov/health/hearing/innear.asp] that convert sound waves into electrical impulses that the auditory nerve carries to the brain. Excessive noise, certain medications, aging, and disease can damage or destroy hair cells. Since the human ear is unable to replace hair cells, our hearing declines as they are lost.

Varying degrees of hearing loss affect more than 36 million American adults. Hair cell regeneration might one day be able to restore hearing, however, researchers say it could take many years to develop a practical method to regrow hair cells in human ears.

Brigande’s recent research demonstrates that it is possible to stimulate growth of hair cells in mouse embryos by transferring the Atoh1 gene into some cells within the developing inner ear. Previous research has shown that Atoh1 can induce hair cell growth, but Brigande’s research represents the first time that gene transfer has produced functioning hair cells in newborn mice. Although not a method to replace adult hair cells, this research advances understanding of hair cell development and provides a useful new technique to other laboratories.

Brigande and his team transferred the Atoh1 gene into developing mouse ears prior to their birth. The Atoh1 gene was paired with a gene coding for green fluorescent protein, a protein that makes a particular jellyfish species glow, and allowed newly formed hair cells to fluoresce green.

One approach to treat hearing loss and deafness is to replace defective cells with healthy new ones, Brigande explains. While his work demonstrates that it is possible to produce functioning hair cells in postnatal mammalian cochlea, he says that further study is needed to determine if gene transfer into a deaf mouse can produce healthy hair cells that enable hearing.

See an abstract of this study online at http://www.nature.com/nature/journal/v455/n7212/abs/nature07265.html. A full text version is available by subscription at http://www.nature.com/nature/journal/v455/n7212/full/nature07265.html.