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St. Jude finds clues to hearing loss from chemotherapy

ions were likely to cause hearing loss, and it was not known which mutation each mouse had. Therefore, the St. Jude team screened more than 1,800 mice from 285 families using an auditory brainstem responses test. This test determines whether a particular mouse can respond to high frequencies by recording electrical activity from the hearing nerve and other parts of the brain in response to brief, high-frequency sounds. The team identified 17 families that showed evidence of hearing loss. The investigators then determined the types of ear abnormalities the mice had. The goal was to find the genes involved in different aspects of hearing loss.

"Now that we've identified the various problems in the ear that can contribute to hearing loss in these models, we can work back and look for specific mutations in these animals," Zuo said. "That will let us link specific mutations to specific disruptions in the ear that cause hearing loss. The long-term goal is to try to manipulate or replace those genes in order to overcome those problems."

Individual mutations might disrupt the work of a cascade of genes that cooperate to construct certain nerves or sections of the inner ear that sense sound; that stimulation is then turned into electrical impulses that go to the hearing center of the brain. Understanding how a specific mutation disrupts that cascade might lead to ways to repair the damage, Zuo said.

For example, one type of damage that occurs in children whose hearing is damaged by chemotherapy is loss of hair cells in the inner part of the ear. These cells sprout extremely fine hairs that move in response to sound waves and set up the electrical impulse that goes into the brain. These are the same cells damaged in adults by prolonged exposure to loud noise. "In the future we'd like to be able to prevent the loss of these hair cells or trigger their re-growth with some form of pharmacological or gene therapy intervention," Zuo said.
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Source:Proceedings of the National Academy of Sciences (PNAS)


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