Mutations in a new scaffold protein Sans cause deafness in Jackson shaker mice

Y. Kikkawa
2003 Human Molecular Genetics  
The Jackson shaker ( js) mouse carries a recessive mutation causing phenotypes such as deafness, abnormal behavior (circling and/or head-tossing) and degeneration of inner ear neuroepithelia. Two alleles have been identified so far, the original js and js seal . A contig of three BAC clones was isolated by positional cloning. Two of the clones rescue the js phenotype by BAC transgenesis. Analysis of transcripts in an overlapping region of the two clones revealed a gene encoding a new
more » ... ke protein, Sans, that showed mutations in the two js mutants. One was a guanine nucleotide insertion in the original js allele and the other a 7-base insertion in the js seal allele. Both insertions are predicted to inactivate the Sans protein by frameshift mutations resulting in a truncated protein lacking the C-terminal SAM domain. Cochlear hair cells in the js murtants show disorganized stereocilia bundles, and Sans were highly expressed in inner and outer hair cells of cochlea. The existence of major motifs, ankyrin repeats and a SAM domain suggests that Sans may have an important role in the development and maintenance of the stereocilia bundles through proteinprotein interaction.
doi:10.1093/hmg/ddg042 pmid:12588793 fatcat:wcrvsv4b45crljl6e4nkgydxgi