title: Mutations in a new scaffold protein Sans cause deafness in Jackson shaker mice.
abstract: 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 scaffold-like 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 mutants 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 protein-protein interaction.
authors.affiliation: Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Tokyo 113-8613, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kikkawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shitara
authors.forename: Shigeharu
authors.initials: S
authors.lastname: Wakana
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kohara
authors.forename: Toyoyuki
authors.initials: T
authors.lastname: Takada
authors.forename: Mieko
authors.initials: M
authors.lastname: Okamoto
authors.forename: Choji
authors.initials: C
authors.lastname: Taya
authors.forename: Kazusaku
authors.initials: K
authors.lastname: Kamiya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tokano
authors.forename: Ken
authors.initials: K
authors.lastname: Kitamura
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Wakabayashi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Shiroishi
authors.forename: Ryo
authors.initials: R
authors.lastname: Kominami
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yonekawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003638:Deafness / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D009419:Nerve Tissue Proteins; C477451:Sans protein, mouse