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Deaf mouse leads scientists to human hearing loss geneBy Kara Gavin / UMHS Public RelationsIn a powerful demonstration of how animal research can help humans, a pair of scientific teams is reporting the discovery of defects in a deafness gene in mice that has led to the identification of similar genetic defects in people with hearing loss. The findings, published in two recent papers, may lead to a screening test and therapy for families affected by one type of inherited hearing loss. The discoveries also bring scientists closer to understanding the intricate choreography of genes and proteins involved in the normal development of human hearing, and the tiny missteps that can destroy hearing even before a baby is born. The discovery of the human deafness gene, called TMIE, is reported in the September issue of the American Journal of Human Genetics. The finding relied on the discovery of a mouse gene, tmie, first reported in the August issue of Human Molecular Genetics. The mouse studies were conducted at the Kresge Hearing Research Institute, part of the U-M Health System (UMHS), using two deaf strains of mice. One mouse strain, called "spinner" because the mice's inner ear problems cause them to spin madly in circles, was found in the 1960s. The other strain used in the study was identified more recently. At U-M, senior author David Kohrman and his colleagues have worked for three years to pinpoint the tmie gene, guided by earlier studies on spinner mice that gave them a general location for searching. Once they found the gene, and the mutations in it that caused deafness in the two strains of mice, they explored how those mutations affect the structure and function of the inner ear, leading to deafness. Researchers think the mutations alter the tiny hair-like stereocilia that coat the hair cells of the inner ear and are crucial to hearing. For years, teams at the University of Iowa and National Institutes of Health (NIH) studied several Indian and Pakistani families with a history of inherited hearing loss. They found the general location of the gene involved in the families' hearing problems, but specific information from the U-M mouse study helped them zero in on it. Using DNA segments made by Kohrman's team to search for similar stretches of DNA in tissue samples from the families, the groups at Iowa and NIH checked for defects in the human TMIE gene. They found three mutations in a day and a half, then found two more each causing hearing loss in one of five different families. "This shows how useful mice are as models for the human ear, and how powerful gene mapping and a classical genetic approach can be," says Kohrman, an assistant professor of otolaryngology at the U-M Medical School. "This gives us an inroad to open up other areas of the genome involved in deafness." Kohrman's colleague Yehoash Raphael, who directs Kresge's Otopathology Laboratory, will continue to aid the research using an electron microscope to see the alterations that tmie mutations cause in the stereocilia of the inner ear's hair cells. The U-M research was supported by the National Institute on Deafness and Other Communication Disorders, the National Organization for Hearing Research and the American Hearing Research Foundation.
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