ENU mutagenesis and the search for deafness genes.

The availability of mouse mutant models for known human deafness loci is limited. Moreover, it is unlikely that the current mouse archives hold mutants for the full panoply of genes involved in auditory system development and transduction. A large-scale ENU mutagenesis is currently underway to increase significantly the number of mouse deafness mutants available, employing specific screens for both deafness and balance defects. In the MRC Harwell screen, 13 mice have been identified so far with deafness, a balance defect or both. Mutagenized mice from the programme are also being used to search for modifiers of a known deafness gene, myosin VIIA (mutated in the Shaker 1 mutant mouse). The progress and encouraging results of the programme indicate that the combination of ENU mutagenesis and effective phenotype screens will lead to a significant contribution to the understanding of the genes and mechanisms involved in hereditary deafness.