Deletion of beaded filament proteins or the C-terminal end of Aquaporin 0 causes analogous abnormal distortion aberrations in mouse lens.
Deletion of beaded filament proteins or the C-terminal end of Aquaporin 0 causes analogous abnormal distortion aberrations in mouse lens.
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DOI：
10.1016/j.exer.2021.108645
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发表时间：
2021-08
影响因子：
3.4
通讯作者：
Kumari, S. Sindhu
中科院分区：
文献类型：
--
作者：
Varadaraj, Kulandaiappan;FitzGerald, Paul G.;Kumari, S. Sindhu
晶状体特异性珠丝（BF）蛋白CP 49和filensin与水通道蛋白水通道蛋白0（AQP 0）的C-末端相互作用。先前我们已经报道了一种C-末端缺失的表达AQP 0的转基因小鼠模型AQP 0 ΔC/ΔC在透镜中产生异常的光学像差。进行这项研究是为了找出BF结构蛋白的总损失是否改变了透镜的光学性质，并引起类似于AQP 0 ΔC/ΔC透镜中的光学像差;另外，在一个实施例中，以绘制在单或双BF蛋白敲除中作为年龄函数的光学质量的变化，以及评估在这些细胞中AQP 0的水通道功能是否存在任何显著变化。击倒对手。通过使CP 49-KO和filensin-KO小鼠杂交，开发了CP 49和filensin的双敲除小鼠（2xKO）模型。通过光轴对不同年龄的野生型、CP 49-KO、filensin-KO和2xKO晶状体以及出生后第17天的AQP 0 ΔC/ΔC晶状体进行成像，并比较光学质量和聚焦特性。所有三种敲除模型均显示透明度丧失，并出现与AQP 0 ΔC/ΔC相似的异常光学畸变像差。在6、9和12个月龄时通过晶状体进行的铜网格聚焦显示，随着年龄的增长，像差增加。随着年龄的增长，所有KO型号的晶状体产生的网格图像显示出从正桶形畸变像差向枕形畸变像差的转变，形成了三个不同的像差区，与AQP 0 ΔC/ΔC晶状体产生的像差区相似。用渗透收缩法测量的由CP 49-KO、filensin-KO和2xKO模型制备的纤维细胞膜囊泡的水渗透性与野生型相似，没有任何统计学显著性改变（P > 0.05）。Western印迹和定量分析显示，在所有三种BF蛋白科斯中，AQP 0的表达量相当。我们的研究表明，单或双珠丝蛋白的损失显着影响透镜的折射率梯度，透明度和聚焦能力在一个年龄依赖性的方式和BF蛋白与AQP 0的相互作用是至关重要的透镜的正常功能。BF蛋白的存在对于防止异常光学像差和维持老化透镜中的稳态是必需的。
Lens-specific beaded filament (BF) proteins CP49 and filensin interact with the C-terminus of the water channel protein Aquaporin 0 (AQP0). Previously we have reported that a C-terminally end-deleted AQP0-expressing transgenic mouse model AQP0ΔC/ΔC developed abnormal optical aberrations in the lens. This investigation was undertaken to find out whether the total loss of the BF structural proteins alter the optical properties of the lens and cause optical aberrations similar to those in AQP0ΔC/ΔC lenses; also, to map the changes in the optical quality as a function of age in the single or double BF protein knockouts as well as to assess whether there is any significant change in the water channel function of AQP0 in these knockouts. A double knockout mouse (2xKO) model for CP49 and filensin was developed by crossing CP49-KO and filensin-KO mice. Wild type, CP49-KO, filensin-KO, and 2xKO lenses at different ages, and AQP0ΔC/ΔC lenses at postnatal day-17 were imaged through the optical axis and compared for optical quality and focusing property. All three knockout models showed loss of transparency, and development of abnormal optical distortion aberration similar to that in AQP0ΔC/ΔC. Copper grid focusing by the lenses at 6, 9 and 12 months of age showed an increase in aberrations as age advanced. With progression in age, the grid images produced by the lenses of all KO models showed a transition from a positive barrel distortion aberration to a pincushion distortion aberration with the formation of three distinct aberration zones similar to those produced by AQP0ΔC/ΔC lenses. Water permeability of fiber cell membrane vesicles prepared from CP49-KO, filensin-KO and 2xKO models, measured using the osmotic shrinking method, remained similar to that of the wild type without any statistically significant alteration (P > 0.05). Western blotting and quantification revealed the expression of comparable quantities of AQP0 in all three BF protein KOs. Our study reveals that loss of single or both beaded filament proteins significantly affect lens refractive index gradient, transparency and focusing ability in an age-dependent manner and the interaction of BF proteins with AQP0 is critical for the proper functioning of the lens. The presence of BF proteins is necessary to prevent abnormal optical aberrations and maintain homeostasis in the aging lens.
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影响因子：
4.4
作者：
Kumari S;Gao J;Mathias RT;Sun X;Eswaramoorthy A;Browne N;Zhang N;Varadaraj K
通讯作者：
Varadaraj K
影响因子：
2.9
作者：
Rose, K. M. Lindsey;Wang, Z.;Schey, K. L.
通讯作者：
Schey, K. L.
DOI：
10.1016/j.bbrc.2019.02.098
发表时间：
2019-04-09
影响因子：
3.1
作者：
Kumari, S. Sindhu;Varadaraj, Kulandaiappan
通讯作者：
Varadaraj, Kulandaiappan
影响因子：
5.9
作者：
Li Z;Gu S;Quan Y;Varadaraj K;Jiang JX
通讯作者：
Jiang JX
影响因子：
3.7
作者：
Gokhin DS;Nowak RB;Kim NE;Arnett EE;Chen AC;Sah RL;Clark JI;Fowler VM
通讯作者：
Fowler VM