- A considerable number (around 35) of new hearing-impaired mouse mutants will be found from mutagenesis programmes.
- All the new mutations will be localised at a low resolution and high resolution genetic maps will be generated for around 25 of these.
- The development of auditory pathology will be investigated in those mutants which are of greatest interest (around 15).
The objective is to double the number of known loci involved in non-syndromic deafness in mice, and to make significant steps towards identifying the responsible genes and understanding the pathological processes leading to hearing impairment. This will be done by adding a new screen for non-syndromic deafness to two large ongoing mutagenesis programmes. Around 35 new hearing-impaired mutants should be found in this way. All the new mutations will be mapped to a mouse chromosome at low resolution, to establish which are new loci and which may be new mutations of known deafness loci. A positional candidate approach to identifying the responsible genes will be initiated in around 25 of the new mutations by generating high resolution (<0.1 cM) genetic maps. Such detailed maps will enable the selection of suitable candidate genes for mutation screening from the rapidly-growing transcript map of the mouse genome. The development of the hearing impairment will be investigated in about 15 new mutants using electrophysiological measures of cochlear function combined with gross structural and ultrastructural study of the middle and inner ear. This information about the phenotype will indicate the cells or tissues which are first affected by the mutation, and help our choice of likely candidate genes for mutation screening, as well as provide a framework for interpreting the molecular basis of the defect when the gene is identified. Finally, both the findings of our work and the mutant mice will be made available to the research community for further study.
Funding SchemeCSC - Cost-sharing contracts
69978 Ramat - Aviv