UI researchers have discovered a deafness-causing gene defect in mice, revealing critical information about a new protein that protects sensory cells in the ear.
When mutated, the gene — known as claudin-9 — is unable to produce normal claudin-9 protein. UI researchers found this protein is critical to maintain proper distribution of potassium in the inner ear. When the gene is mutated, potassium floods the wrong part of the sensory cells, killing most of them and leaving remaining cells defective, according to the research.
Botond Banfi, assistant professor of anatomy and cell biology, served as the senior author of the report.
Sensory cells in the ear work in a “dangerous environment,” Banfi said.
“One side of the cells is exposed to a high potassium solution, the other to a low potassium solution, and they are insulated from each other. If the insulator is defective, sensory cells become damaged,” he said. “The discovery explains how cells in the hearing organ survive.”
Banfi said the study — which includes assistance from The Jackson Laboratory in Bar Harbor, Maine and the Kansas State University research laboratory — took nearly three years to complete.
“The study required careful characterization,” Banfi said of the laboratory collaboration. “The collaboration required technical approaches used at the [other] laboratories.”
Banfi and his colleagues, including UI assistant research scientist Yoko Nakano, are screening people with hearing impairment to see if some have the mutation in claudin-9. After screening many patients, Banfi expects to find the mutation in a small number of patients.
While Banfi said the findings will not cure deafness, the mouse models used in testing are similar to human auditory genetics, providing unprecedented research into the human hearing organ.
“The mouse has turned out to be a very accurate model in human hearing,” Banfi said. “It also provides knowledge of how the hearing organ works.”
Banfi and his colleagues are looking into future research on the protein.
“The claudin-9 protein is part of a large complex,” Banfi said. “We are interested in finding other components of the complex.”
Hereditary deafness is one of the most common birth defects in humans. According to the National Institute of Deafness and Other Communication Disorders, roughly 2 to 3 out of every 1,000 children in the United States are born deaf or hard-of-hearing, and nine out of every 10 children born deaf have parents who can hear.
“The significance of all UI findings is enormous,” said Jeanne Prickett, superintendent of the Iowa School for the Deaf. “They’ve done excellent research in hearing impairment and the root causes of hearing impairment.”
The UI researchers’ findings appeared in the Aug. 21 issue of the journal PLoS Genetics. The study was partially funded by a grant from the National Institutes of Health and supported by the UI Carver College of Medicine in the UI Gene Therapy Center.