A gene defect that makes some mice appear to be dancing to their own tune has been mapped to a specific gene, according to an article in the Aug. 4 issue of the journal Cell.
A group led by Northwestern University Medical School researcher James R. Bartles mapped the deafness mutation in "jerker" mice to a gene that makes cells produce a protein called espin. The espin protein, which is present in a number of places in the nervous system, is a key component of stereocilia of hair cells, the apparatus in the inner ear that detects sound and motion and helps control balance in the body.
The espin gene mutation Bartles and colleagues found in the jerker mouse causes hair cell degeneration, deafness and vestibular (inner ear) dysfunction.
Jerker mice also exhibit such behaviors as hyperactivity, running in tight circles and head tossing, which are presumed to be the result of defects in the hair cells of the vestibular system.
Bartles believes that in these mice, the mutated espin gene causes vestibular hair cells to send false signals to the brain, in effect telling the animal it is falling or circling in one direction (for example, to the left), when it really isn’t. To compensate, the brain tells the mouse to turn in the opposite direction (in this case, to the right).
Interestingly, the mutated form of the espin gene is a single-point mutation, that is, a change of one base in the protein’s DNA sequence.
"I personally find it fascinating that this single point mutation in the espin gene can give rise to such pronounced deficits at the behavioral level," Bartles said.
Bartles and his laboratory team discovered espins several years ago, first in intercellular junctions in the testis and later in the kidney and intestine.
"Because espins were originally discovered in these organs, we never would have guessed that these proteins would be so important for the functioning of hair cells in the inner ear," Bartles said.
Bartles and colleagues are in the process of studying the espin gene in other animals, including humans. This information may one day be used to identify a population of humans with deafness or balance disorders that can be ascribed to the espin gene.
Bartles is an associate professor of cell and molecular biology at the Medical School and a member of the Northwestern University Institute for Neuroscience. His co-authors on this article were Lili Zheng, Gabriela Sekerkova and Enrico Mugnaini, M.D., director of the Northwestern University Institute for Neuroscience and professor of cell and molecular biology. Lewis G. Tilney and Kelly Vranich, of the University of Pennsylvania, Philadelphia, also were co-authors.
The espin gene discovery is another in a series of hearing-related genes mapped by researchers at Northwestern University. In May, Peter Dallos, Hugh Knowles Professor of Hearing Sciences and John Evans Professor of Neuroscience, and Laird D. Madison, M.D., assistant professor of medicine, cloned the gene for prestin, a protein that is critical to the functioning of the outer hair cell, a sensory receptor cell unique to the inner ear of mammals.
Journal
Cell