Aberrant retinal tight junction and adherens junction protein expression in an animal model of autosomal recessive Retinitis pigmentosa: The Rho(-/-) mouse
Aberrant retinal tight junction and adherens junction protein expression in an animal model of autosomal recessive Retinitis pigmentosa: The Rho(-/-) mouse
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DOI：
10.1016/j.exer.2006.01.032
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发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Brankin, B.
中科院分区：
文献类型：
--
作者：
Campbell, M.;Humphries, M.;Brankin, B.
视网膜色素变性（RP）包括一组异质性遗传性疾病，其特征在于视网膜中的视杆光感受器的原发性变性和视锥光感受器的继发性变性。其他病理变化包括血管变化和视网膜色素上皮（RPE）细胞对视网膜内层的侵入。RP是全球进行性视网膜疾病的主要原因。使用小鼠模型的常染色体显性视网膜色素变性（adRP）与视网膜病变的视紫红质基因Rho（-/-）的有针对性的破坏诱导，我们分析了一系列的紧密连接和粘附连接相关蛋白的表达水平，以进一步阐明发生在这种情况的早期阶段的致病机制。使用来自C-129背景的6周龄小鼠的视网膜冷冻切片的蛋白质印迹分析和间接免疫染色，我们已经确定了一系列紧密连接和粘附连接相关蛋白的表达和定位水平的变化，如果有的话，包括闭锁小带-1（ZO-1）、闭合蛋白、N-钙粘蛋白、p120-连环蛋白、α-连环蛋白、γ-连环蛋白、β-连环蛋白和E-钙粘蛋白。我们发现，与6周龄野生型（WT）小鼠相比，6周龄Rho（-/-）基因敲除小鼠的神经视网膜中紧密连接和粘附连接相关蛋白封闭带-1（ZO-1）上调。然而，在免疫组织化学之后，与相同年龄的WT动物相比，Rho（-/-）视网膜的外界膜（OLM）处的ZO-1、β-连环蛋白和p120-连环蛋白表达似乎部分受损。我们推测这些视网膜感光细胞死亡后的变化可能有助于adRP的发病机制。我们发现6周龄Rho（-/-）小鼠OLM中ZO-1和相关粘附连接蛋白β-连环蛋白和p120-连环蛋白表达水平的变化，为常染色体显性RP（adRP）动物模型中紧密连接和粘附连接相关蛋白修饰提供了证据。(c)2006爱思唯尔有限公司保留所有权利。
Retinitis pigmentosa (RP) comprises a heterogenous group of inherited diseases that are characterised by primary degeneration of rod photoreceptors and secondary degeneration of cone photoreceptors in the retina. Additional pathological changes include vascular changes and invasion of the inner retina by retinal pigment epithelial (RPE) cells. RP represents a major cause of progressive retinal disease worldwide. Using a mouse model of autosomal dominant Retinitis pigmentosa (adRP) with retinopathy induced by targeted disruption of the rhodopsin gene Rho(-/-), we have analysed the levels of expression of a range of tight and adherens junction associated proteins, in order to further elucidate the pathogenic mechanisms occurring at an early stage of this condition. Using western blot analysis and indirect immunostaining of retinal cryosections from 6-week-old mice from a C-129 background we have determined changes, if any, in the levels of expression and localisation of a series of tight and adherens junction associated proteins, including Zonula Occludens-1 (ZO-1), occludin, N-Cadherin, p120-Catenin, alpha-Catenin, gamma-Catenin, beta-Catenin, and E-Cadherin. We have found an up-regulation of the tight junction and adherens junction associated protein Zonula Occludens-1 (ZO-1) in the neural retina of 6-week-old Rho(-/-) knockout mice compared with 6-week-old Wild-Type (WT) mice. Following immunohistochemistry, however, it appears, that ZO-1, beta-Catenin and p120-Catenin expression at the Outer Limiting Membrane (OLM) of the Rho(-/-) retina is compromised, in part, compared to WT animals of the same age. We hypothesise that these retinal changes following photoreceptor cell death may contribute to the pathogenesis of adRP. Our findings of changes in the levels of expression of ZO-1 and associated adherens junction proteins beta-Catenin and p120-Catenin at the OLM in 6-week-old Rho(-/-) mice provide evidence for tight junction and adherens junction associated protein modifications in an animal model of autosomal dominant RP (adRP). (c) 2006 Elsevier Ltd. All rights reserved.