Culminating several years of work, scientists at the University of Washington have identified a gene that, when mutant, causes mice to be deaf and to suffer from motor imbalance.
Aptly named, these "deafwaddler" mice lack a protein that transports calcium ions across the plasma membranes of the hair cells. The hair cells transduce sound and control balance in the auditory and vestibular systems of the inner ear.
The research is published in the August issue of Nature Genetics.
Based on the fact that the auditory systems of mice and humans are very similar, researchers led by Dr. Bruce Tempel, UW associate professor of otolaryngology-head and neck surgery, plan to extend their studies on deafwaddler mice to examine heritable forms of deafness and vertigo in humans.
"We study the genes that cause deafness in mice because we can control the genetic background of mice, thereby allowing us to make the jump to humans from a well-examined model organism," said Tempel. Studies on other mouse mutants have predicted several human deafness genes and have identified new genes that turn out to be critical for normal hearing.
Identification of the gene mutated in the deafwaddler mice is especially interesting to auditory scientists, because the mutation affects the physiological function of hair cells, but leaves them morphologically (structurally) intact. Previously identified genes that cause deafness in mice or humans cause structural changes, resulting in hair cells that never form or develop abnormally.
The deafwaddler mutation affects the ability of the plasma membrane of the cell to transport calcium, which is essential to normal cell function. The ability of the membrane to regulate the cell's electrical charge is compromised, specifically affecting the calcium balance in the cell. Thus, the hair cell's ability to transduce information to the auditory nerve about sound and position is compromised, resulting in deafness and vertigo.
Having identified the mutated gene in the mouse, the researchers are now working to find the gene in humans. They will analyze members of families where there is both deafness and dizziness, to determine whether they have a mutation in the equivalent human gene.
While finding the gene may not lead to immediate treatment, the researchers hope the discovery will aid in the development of new pharmacological or gene therapies for people with deafness and vertigo. The deafwaddler mouse will provide a unique genetic model for testing these new therapies.
Co-authors of the study are Drs. Valerie A. Street, Jennifer W. McKee-Johnson and Rosalia C. Fonseca, all of the Virginia Merrill Bloedel Hearing Research Center and the UW Department of Otolaryngology-Head and Neck Surgery; and Dr. Konrad Noben-Trauth of the National Institute on Deafness and Other Communication Disorders.
The research was supported by grants from the NIH and the NIDCD Division of Intramural Research.