The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice.
The R109H variant of fascin-2, a developmentally regulated actin crosslinker in hair-cell stereocilia, underlies early-onset hearing loss of DBA/2J mice.
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DOI：
10.1523/jneurosci.1541-10.2010
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发表时间：
2010-07-21
期刊：
影响因子：
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通讯作者：
Johnson KR
中科院分区：
文献类型：
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作者：
Shin JB;Longo-Guess CM;Gagnon LH;Saylor KW;Dumont RA;Spinelli KJ;Pagana JM;Wilmarth PA;David LL;Gillespie PG;Johnson KR
数量性状基因座ahl 8是DBA/2 J小鼠早发性年龄相关性听力损失的关键因素。小鼠肌成束蛋白-2基因（Fscn 2）中的非同义核苷酸取代是造成这种表型的原因，这一点通过野生型BAC转基因挽救DBA/2 J小鼠的听力损失得到了证实。在鸡和小鼠中，FSCN 2蛋白在毛细胞静纤毛中是丰富的，该富含肌动蛋白的结构包括机械敏感的毛束，并且集中在毛束最长静纤毛的静纤毛尖端。当这些静纤毛差异伸长时，FSCN 2表达增加，表明FSCN 2控制细丝生长，使暴露的静纤毛变硬，或两者兼而有之。因为ahl 8仅在突变钙粘蛋白23存在时加速听力损失，而钙粘蛋白23是毛细胞尖端连接的一个组成部分，所以机械转导和肌动蛋白交联在功能上必须是相互关联的。
The quantitative trait locus ahl8 is a key contributor to the early-onset, age-related hearing loss of DBA/2J mice. A non-synonymous nucleotide substitution in the mouse fascin-2 gene (Fscn2) is responsible for this phenotype, confirmed by wild-type BAC transgene rescue of hearing loss in DBA/2J mice. In chickens and mice, FSCN2 protein is abundant in hair-cell stereocilia, the actin-rich structures comprising the mechanically sensitive hair bundle, and is concentrated towards stereocilia tips of the bundle's longest stereocilia. FSCN2 expression increases when these stereocilia differentially elongate, suggesting that FSCN2 controls filament growth, stiffens exposed stereocilia, or both. Because ahl8 accelerates hearing loss only in the presence of mutant cadherin 23, a component of hair-cell tip links, mechanotransduction and actin crosslinking must be functionally interrelated.