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Changes in Gene Expression Profiling and Phenotype in Aged Multidrug Resistance Protein 4-Deficient Mouse Retinas

机译:老化多药抗性蛋白4缺乏小鼠视网膜中基因表达分析和表型的变化

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摘要

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the coeffects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of mouse retinas. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same conditions to 8–12 weeks (young) or 45–55 weeks (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to aged WT mice, and subsequent gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision and transcellular barrier functions that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the four age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.
机译:多药抗性蛋白4(MRP4)是一种能量依赖性膜转运蛋白,其负责广泛的异卵和生理基质的细胞流出。在该试验中,我们旨在使用小鼠视网膜的基因表达微阵列和形态学和电生理学分析来研究老龄化和MRP4缺乏的系数。 MRP4-敲除(零)小鼠和野生型(WT)小鼠在相同的条件下饲养至8-12周(年轻)或45-55周(年龄)。微阵列分析鉴定了来自老年人MRP4-禁止小鼠的视网膜的不同表达基因,与年龄的WT小鼠相比,随后的基因本体论和Kegg途径分析表明,不同表达的基因与镜片,眼睛发育,视觉和透气屏障功能有关参与代谢途径或病毒感染途径。对于年轻/老年的WT小鼠和年轻/老年MRP4-零小鼠的每个视网膜层,观察到厚度明显变化。此外,视网膜细胞类型的免疫组织化学分析没有表现出四种年龄/基因型组的细胞形态或分布的明显变化,并且电气图术反应显示出老化的WT小鼠和老化MRP4之间的振幅或潜伏期没有显着差异。零老鼠。在MRP4缺乏存在下,老化将是对视网膜造成一些损害的压力不足。

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