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St. Jude finds clues to hearing loss from chemotherapy

Children with cancer who suffer hearing loss due to the toxic effects of chemotherapy might one day be able to get their hearing back through pharmacological and gene therapy, thanks to work done with mouse models at St. Jude Children's Research Hospital. Mice with a variety of genetic mutations that disrupt different parts of the ear will also help scientists understand age-related hearing loss in adults, as well as hearing loss caused by long-term exposure to loud noise, according to the researchers.

The investigators took the first step toward these ambitious goals by identifying 17 families of mice whose offspring carry one or more of a variety of mutations that cause them to lose the ability to hear high-frequency sounds, according to Jian Zuo, Ph.D., associate member of the St. Jude Department of Developmental Neurobiology. Zuo is senior author of a report on this work that appears in the October issue of Hearing Research.

These models will help scientists understand what happens in the ears of children who suffer ototoxicity (toxic damage to the inner ear due to chemotherapy) and eventually, which genes are responsible for that damage. "Our ongoing study of these mouse models will advance understanding of age-related and noise-induced hearing loss in humans--such as long-term exposure to loud music--which are similar to the damage that occurs in children receiving chemotherapy," Zuo said.

The mouse models of hearing loss were produced by the Tennessee Mouse Genome Consortium, a group of institutions across Tennessee that includes universities, several medical research centers and a national laboratory.

The consortium used ENU, a chemical that causes random mutations in sperm of mice that were subsequently mated with females. Offspring of this mating carried mutations in one or more specific spots in their DNA, Zuo explained. The random mutations caused a variety of disruptions of normal functions. However, only some of the mutat
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Source:Proceedings of the National Academy of Sciences (PNAS)


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