Deaf mouse leads scientists to human
hearing loss gene
By Kara Gavin / UMHS Public Relations
In 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
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
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 moreáeach
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.