Mutations in a new scaffold protein Sans cause deafness in Jackson shaker mice.
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.
Kikkawa
Yoshiaki
Y
Department of Laboratory Animal Science, The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Tokyo 113-8613, Japan.
Shitara
Hiroshi
H
Wakana
Shigeharu
S
Kohara
Yuki
Y
Takada
Toyoyuki
T
Okamoto
Mieko
M
Taya
Choji
C
Kamiya
Kazusaku
K
Yoshikawa
Yasuhiro
Y
Tokano
Hisashi
H
Kitamura
Ken
K
Shimizu
Kunihiko
K
Wakabayashi
Yuichi
Y
Shiroishi
Toshihiko
T
Kominami
Ryo
R
Yonekawa
Hiromichi
H
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
D009419:Nerve Tissue Proteins; C477451:Sans protein, mouse