ERM proteins as integrators at the cell cortex : Gene knockout study

我们发现，在成年野生型小鼠的耳蜗和前庭感觉毛细胞中，放射素特异性地富含在立体纤毛中，这是一种特殊发育的巨型微绒毛，而辐射缺乏的成年小鼠表现为耳聋，但没有明显的前庭功能障碍。在听力发病年龄前(~2周)，在RDX^&lt；-/-&gt；小鼠的耳蜗和前庭，立体纤毛发育正常，其中以Ezrin代替Radioxin。随着这些RDX^&lt；-/-&gt；小鼠的成长，基于Ezrin的耳蜗体纤毛逐渐退化，导致耳聋，而在成年RDX^&lt；-/-&gt；小鼠中，基于Ezrin的前庭立体纤毛保持正常。因此，我们得出结论，辐射对小鼠的听力是不可或缺的，它通过维持曾经发展起来的耳蜗静纤毛。Ezrin基因敲除引起的失语症：胃尖部小管形成/扩张的缺陷…更多的壁细胞胃酸分泌丧失在病理学上被称为胃酸过多。分泌酸性的壁细胞的特征是大量表达Ezrin(Vil2)，它是ERM(Ezrin/Radioxin/Moesin)蛋白之一，通常使肌动蛋白细丝与质膜蛋白交联。在这里，我们展示了Ezrin在体内直接参与胃酸分泌。Ezrin基因敲除(Vil2^&lt；-/-&gt；)小鼠在出生后存活不到一周，这使得检测胃酸分泌变得困难。然后，我们通过在外显子2和3之间引入新霉素抗性盒，获得了Ezrin基因敲除小鼠(Vil2^&lt；kd/kd&gt；)。按预期孟德尔比率出生的Vil2^&lt；kd/kd&gt；小鼠表现出生长迟缓和高死亡率。大约7%的小鼠存活到成年。Vil2^&lt；kd/kd&gt；胃中Ezrin蛋白水平下降到野生型水平的5%，而没有RADX或moesin的补偿性上调。成年Vil2^&lt；kd/kd&gt；小鼠出现严重的酸中毒。免疫荧光和电子显微镜显示，胃壁细胞管状顶膜的形成/扩张存在缺陷，引起胃酸过多。较少

Radixin deficiency causes deafness associated with progressive degeneration of cochlear stereociliaWe found that, in cochlear and vestibular sensory hair cells of adult wild-type mice, radixin was specifically enriched in stereocilia, specially-developed giant microvilli, and that radixin-deficient (Rdx^<-/->) adult mice exhibited deafness but no obvious vestibular dysfunction. Before the age of hearing onset (〜2 weeks), in the cochlea and vestibule of Rdx^<-/-> mice, stereocilia developed normally in which ezrin was concentrated instead of radixin. As these Rdx^<-/-> mice grew, ezrin-based cochlear stereocilia progressively degenerated, causing deafness, whereas ezrin-based vestibular stereocilia were maintained normally in adult Rdx^<-/-> mice. We thus concluded that radixin is indispensable for the hearing ability in mice through the maintenance of cochlear stereocilia, once-developed.Achlorhydria by ezrin knockdown : defects in the formation/expansion of apical canaliculi in gastri … More c parietal cellsLoss of gastric acid secretion is pathologically known as achlorhydria. Acid-secreting parietal cells are characterized by abundant expression of ezrin (Vil2), one of ERM (ezrin/radixin/moesin) proteins, which generally cross-link actin filaments with plasma membrane proteins. Here we show the direct in vivo involvement of ezrin in gastric acid secretion. Ezrin-knockout (Vil2^<-/->) mice did not survive more than one week after birth, making difficult to examine gastric acid secretion. We then generated ezrin-knockdown (Vil2^<kd/kd>) mice by introducing a neomycin resistance cassette between exons 2 and 3. Vil2^<kd/kd> mice born at the expected Mendelian ratio exhibited growth retardation and a high mortality. 〜7% of Vil2^<kd/kd> mice survived to adulthood. Ezrin protein levels in Vil2^<kd/kd> stomachs decreased to <5% of the wild-type levels without compensatory up-regulation of radixin or moesin. Adult Vil2^<kd/kd> mice suffered from severe achlorhydria. Immunofluorescence and electron microscopy revealed that this achlorhydria was caused by defects in the formation/expansion of canalicular apical membranes in gastric parietal cells. Less