Mutations in a new scaffold protein Sans cause deafness in Jackson shaker mice
Mutations in a new scaffold protein Sans cause deafness in Jackson shaker mice
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DOI：
10.1093/hmg/ddg042
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发表时间：
2003-03-01
影响因子：
3.5
通讯作者：
Yonekawa, H
中科院分区：
文献类型：
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作者：
Kikkawa, Y;Shitara, H;Yonekawa, H
杰克逊摇瓶（shaker）小鼠携带隐性突变，该隐性突变引起表型，例如耳聋、异常行为（转圈和/或摇头）和内耳神经上皮退化。到目前为止，已经发现了两个等位基因，原始的js和js（seal）。通过定位克隆分离三个BAC克隆的重叠群。两个克隆通过BAC转基因挽救了js表型。在两个克隆的重叠区域中的转录分析揭示了编码新的支架样蛋白Sans的基因，该基因在两个js突变体中显示突变。一个是在原始的js等位基因中插入鸟嘌呤核苷酸，另一个是在Js（密封）等位基因中插入7个碱基。预测两个插入都通过移码突变使Sans蛋白变性，从而导致缺乏C-末端SAM结构域的截短蛋白。Js murtants耳蜗毛细胞静纤毛束排列紊乱，Sans在耳蜗内、外毛细胞中高表达。主要基序，锚蛋白重复序列和SAM结构域的存在表明，Sans可能通过蛋白质-蛋白质相互作用在静纤毛束的发育和维持中发挥重要作用。
The Jackson shaker (is) 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 transcriois 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 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 protein-protein interaction.