Behavioral audiograms of homozygous med(J) mutant mice with sodium channel deficiency and unaffected controls.

Complete behavioral audiograms were determined for med(J) mice (F1 offspring of C57BL/6JxC3HeB/FeJ) and unaffected controls from the same F1 background. The med(J) mutation results in greatly reduced levels of Scn8a voltage-gated sodium channels, which causes abnormal conduction of action potentials throughout the nervous system and may account for the virtual absence of spontaneous bursting activity in the dorsal cochlear nucleus. The med(J) mice also have tremors, display dystonic postures, and drag their hind legs. The mice were tested using a conditioned suppression/avoidance procedure, with minor modifications of the apparatus made to accommodate the motor-impaired med(J) mice. Thresholds were repeatedly obtained up to the age of 50 weeks to determine if the animals developed a hearing loss with age. The results indicate that med(J) mice have normal thresholds, with the first signs of hearing loss (detectable at 80 kHz) appearing for both the med(J) and normal mice by 48 weeks. Neither the med(J) nor the normal mice could hear below 1 kHz, indicating that house mice fall into the group of mammals with poor low-frequency hearing. The results also demonstrate that the conditioned suppression/avoidance procedure is well suited for assessing hearing in severely impaired, as well as normal, mice and that it can provide for the rapid determination of thresholds necessary to follow changes in hearing that may occur as the result of age, disease, mutation, or drugs.