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Increasing Protein Level Rescues Hearing in Deaf Mice

A new study in mice gives insight into the cause behind many cases of deafness and suggests new therapeutic approaches to combating hearing loss.

Over half of the cases of genetic hearing loss in some populations are caused by mutations in the genes for a family of proteins known as connexins. Connexins span the membranes of cells and create connections between them called gap junctions. Gap junctions allow molecules to pass freely through them, and are important for cell communication.

Two connexins, Cx26 and Cx30, are most commonly associated with hearing loss. They’re the two major connexins found in the gap junctions between supporting cells that surround hair cells in the cochlea, part of the inner ear. When either is missing, the gap junctions fail to work, and the cochlea's hair cells die off, leaving the inner ear incapable of translating sounds into nerve impulses. Why both Cx26 and Cx30 are needed to create functional gap junctions, however, has been something of a puzzle. Mice without one or the other protein still have gap junctions, albeit comprised of just one of the proteins.

Dr. Xi Lin of the Emory University School of Medicine led a team investigating whether both connexins are necessary to make functional gap junctions. If it was simply an insufficient amount of connexin that causes deafness, then the problem might be corrected by increasing the amount of the remaining one. With funding from NIH's National Institute on Deafness and Other Communication Disorders (NIDCD) and other sources, the team tested whether the hearing of deaf mice without Cx30 could be restored by creating transgenic mice that make higher levels of Cx26

In the January 23, 2007, issue of the Proceedings of the National Academy of Sciences, the researchers described how they transferred extra copies of the Cx26 gene into mice lacking Cx30. The extra Cx26, the researchers discovered, prevented hair cell death and completely restored hearing to the deaf mice. The result shows that gap junctions don't have to contain both Cx26 and Cx30 for normal hearing.

Lin explained, "The problem is simply caused by not having enough protein remaining in the ear of these mutant mice to assemble gap junctions." He and his colleagues are now working to see if increasing Cx30 can likewise help when Cx26 is absent.

This study suggests new therapeutic strategies for patients with connexin-linked deafness. One day, treatments that help cells in the cochlea produce more Cx26 or slow down it's degradation might prevent and treat deafness caused by Cx30 mutations, and vice versa.

— by Harrison Wein, Ph.D.