University of Virginia Health System

RESEARCHERS FIND KEY MOLECULAR CLUE TO INHERITED DEAFNESS

Study Also Identifies Strategy for Discovering Other Gene Functions

Scientists at the University of Virginia Health System have identified the role of a protein molecule that may be critical for normal hearing and balance. The cover article of today's journal Cell describes the results of a study that compared how a type of protein, called myosin Ic, controls the function of sensory hair cells in the ears of genetically engineered mice versus normal mice.

The hair cells of a mouse are remarkably similar to those of a human, said the study's leading author, Jeffrey R. Holt, assistant professor in the U.Va. Department of Neuroscience and Otolaryngology. Our study was based on previous research that showed an association with deafness and mutation in four types of myosin molecules found in the ear's sensory cells.

The inner ear contains cells with hair-like elongations that bend in response to stimuli such as sound and head movements. The cells constantly adapt to stimuli by sending signals to the brain that help people stay oriented if they tilt their head, for example. With sound, hair cells react to sound waves, transmitting signals that enable the brain to process a huge range of frequencies and volumes, from a pin dropping to a cannon booming.

When a mutation exists in a hair cell's myosin proteins, signals to the hair cells may not be transmitted, Holt said. For this study, the researchers isolated and observed the function ofone myosin molecule, myosinIc, by making it sensitive to a drug that affected none of the other myosin molecules. The drug (2-methyl butyl adenosine diphosphate) inihibited the molecule (Y61G-MyoIc), revealing abnormal adaptation of the hair cells of the genetically engineered mice.

The sensory tissue from each group of mice was tested in a specially built recording chamber with a microscope to view and measure the hair cells' response to sound waves using a small glass electrode. Another electrode moved the hair cells back and forth to generate the signal that would be sent to the brain during a head movement. The normal cells were able to adapt repeatedly to the changes created by the stimuli, although the genetically engineered mouse cells were not.

In humans, there are 40 different myosins, and we can now apply this tool and start to figure out the puzzle of what each of them do in future research, Holt said. Once we identify these myosins and know what their role is and understand how they're working in deafness, we hope to be able to take the correct form of the gene, put it into a biological vector, and 'infect' the unhealthy cells so that hearing may be rescued. That's the goal for what might be a clinical application 10 years from now.

The study was funded by the National Institute on Deafness and Other Communication Disorders at the National Institutes of Health, and conducted in collaboration with the Oregon Health and Science University, the McLaughlin Research Institute of Montana, the University of the California-San Francisco and Harvard Medical School.

For a full list of authors, please go to: http://www.cell.com/cgi/content/abstract/108/3/371

February 7, 2002