International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


Taylor A 1, Cheong MA 2, Bussoli TJ 2, Kelly A 2, Steel KP 1

1 Wellcome Trust Sanger Institute, Cambridge, United Kingdom, 2 MRC Institute of Hearing Research, Nottingham, United Kingdom

bronx waltzer is an autosomal recessive mouse mutation causing abnormalities in the inner ear which result in mutant mice having deficiencies in both the auditory and vestibular systems. Homozygous mice exhibit hyperactivity, circling behaviour, head tossing and failure to respond to sound. Hearing loss in these mice is due to degeneration of the inner hair cells in the organ of Corti, while the vestibular phenotype is a result of sensory hair cell degeneration in the maculae and cristae. This phenotype is visible from E17.5, shortly after the hair cells differentiate, making bronx waltzer an interesting model for the understanding of the molecular basis of development and function of the inner ear as well as for hereditary deafness.

The mutation is being mapped using a backcross of 1085 mice to the inbred strain 101/H and has been localised to a 1.9Mb region of chromosome 5 between 113.5Mb and 115.4Mb which contains 49 genes in Ensembl Build32. There remain 17 backcross mice with recombinations within this interval but we have been unable to find new markers polymorphic for the two strains, a task made difficult because bronx waltzer arose spontaneously and is maintained on an unknown background. We have carried out sequence sampling of over 200 amplicons in areas where polymorphisms might be expected such as 3’UTRs, tandem repeats and reported SNPs and have found the sequences of the two strains to be remarkably similar in this region.

As a result of the difficulties encountered with refining the localisation of the mutation we are pursuing alternative approaches to identifying the gene responsible for the bronx waltzer phenotype. These include assessment of the candidacy of genes in the region by in situ hybridisation and screening for replication of the phenotype in zebrafish on injection of morpholinos designed to the fish orthologs of mouse candidates. We are also carrying out large scale exon resequencing of the genes in the region to identify the mutation at the sequence level.

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