Analysis of subcellular localization of Myo7a, Pcdh15 and Sans in Ush1c knockout mice.
Analysis of subcellular localization of Myo7a, Pcdh15 and Sans in Ush1c knockout mice.
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DOI：
10.1111/j.1365-2613.2010.00751.x
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发表时间：
2011-02
影响因子：
3
通讯作者：
Liu XZ
中科院分区：
文献类型：
--
作者：
Yan D;Kamiya K;Ouyang XM;Liu XZ
Usher综合征（Usher syndrome，USH）是人类最常见的致盲性疾病，小鼠模型和分子生物学研究的一个重要发现是USH蛋白整合到一个调控内耳形态发生的蛋白质网络中。为了进一步了解harmonin在USH 1发病机制中的作用，我们建立了一个靶向无效突变Ush 1c小鼠模型。在这里，我们检查无效突变的Ush 1c基因的亚细胞定位的Myo 7a，Pcdh 15和Sans在内耳的影响。在Ush 1c-/-和Ush 1c-/+对照小鼠的耳蜗切片和全标本中分析形态学和蛋白质分布。我们在敲除小鼠和对照小鼠中观察到Myo 7a在整个细胞质中的相同分布。然而，我们检测到Pcdh 15在基地的静纤毛和表皮板在耳蜗毛细胞从Ush 1c +/-对照，而在敲除Ush 1c-/-小鼠，Pcdh 15染色集中在顶端区域的外毛细胞和没有明确的染色检测到在基地的静纤毛，也没有在表皮板。我们发现Sans定位于对照小鼠耳蜗毛细胞的静纤毛中。然而，在Ush 1c-/-小鼠的耳蜗中，检测到强Sans信号朝向静纤毛基部靠近它们插入表皮板的插入点。我们的数据表明，由harmonin的缺乏引起的USH 1网络的解体，可能导致原钙粘蛋白15和Sans蛋白在Ush 1c-/-敲除小鼠耳蜗毛细胞中的错误定位。
Usher syndrome (USH) is the most frequent cause of combined deaf-blindness in man. An important finding from mouse models and molecular studies is that the USH proteins are integrated into a protein network that regulates inner ear morphogenesis. To further understand the function of harmonin in the pathogenesis of USH1, we have generated a targeted null mutation Ush1c mouse model. Here, we examine the effects of null mutation of the Ush1c gene on subcellular localization of Myo7a, Pcdh15 and Sans in the inner ear. Morphology and proteins distributions were analyzed in cochlear sections and whole mount preparations from Ush1c-/- and Ush1c-/+ controls mice. We observed the same distribution of Myo7a throughout the cytoplasm in knockout and control mice. However, we detected Pcdh15 at the base of stereocilia and in the cuticular plate in cochlear hair cells from Ush1c+/- controls, whereas in the knockout Ush1c-/- mice, Pcdh15 staining was concentrated in the apical region of the outer hair cells and no defined staining was detected at the base of stereocilia nor in the cuticular plate. We showed localization of Sans in the stereocilia of controls mouse cochlear hair cells. However, in cochleae from Ush1c-/- mice, strong Sans signals were detected toward the base of stereocilia close to their insertion point into the cuticular plate. Our data indicate that the disassembly of the USH1 network caused by absence of harmonin, may have led to the mis-localization of the Protocadherin 15 and Sans proteins in the cochlear hair cells of Ush1c-/- knockout mice.
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影响因子：
9.8
作者：
Ahmed, ZM;Riazuddin, S;Wilcox, ER
通讯作者：
Wilcox, ER
影响因子：
4
作者：
El-Amraoui, A;Petit, C
通讯作者：
Petit, C
DOI：
10.1083/jcb.137.6.1287
发表时间：
1997-06-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hasson T;Gillespie PG;Garcia JA;MacDonald RB;Zhao Y;Yee AG;Mooseker MS;Corey DP
通讯作者：
Corey DP
DOI：
10.1073/pnas.1130432100
发表时间：
2003-05-27
影响因子：
11.1
作者：
Gibbs, D;Kitamoto, J;Williams, DS
通讯作者：
Williams, DS
影响因子：
3.5
作者：
Alagramam, KN;Yuan, HJ;Smith, RJH
通讯作者：
Smith, RJH