The researchers studied mice that lacked both copies of Ink4d (Ink4d -/- mice; normally, one copy of each gene is inherited from each parent). Using biochemical techniques that highlighted hair cells under the microscope, they observed hair cell loss in mice that were 2.5 weeks old. When the Ink4d -/- mice were seven weeks old, hair cell loss had progressed even further. Specifically, the innermost of four rows of sensory hair cells suffered a loss of 43.3% of cells, and the three outer rows suffered losses of 27.8%, 8.1%, and 8.5%, respectively. Mice that had both copies of the Ink4d gene (Ink4d +/+) did not suffer loss of sensory hair cells in the organ of Corti.

The researchers also used sound measurements to test how well the mice responded to sound. One test, called "distortion product otoacoustic emission" (DPOAE) measures sounds generated by the hair cells themselves in response to being stimulated by sound waves coming into the inner ear. The DPOAE test was performed at weeks 7 and 15 in both Ink4d +/+ and Ink4d -/- mice. The ears of normal mice produced normal responses to sound waves entering the ear, but the ears of mice lacking Ink4d did not respond to this stimulation.

In addition, the investigators used a test called "auditory brainstem response" (ABR) to compare the nerve response to sound in mice with and without Ink4d. The ABR test studies the electric impulses of the auditory nerve pathways from the ear in response to clicks or short bursts of sound. Specifically, it measures the so-called "sound pressure level (SPL)," or the strength a stimulus must be before there is a measurable response in these nerves. At 7 weeks of age the Ink4d -/- mice had responses similar to Ink4d +/+ mice. However, by week 15, the sound level had to be increased signi
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Contact: Bonnie Cameron
bonnie.cameron@stjude.org
901-495-4815
St. Jude Children's Research Hospital
1-May-2003