A hybrid photoreceptor expressing both rod and cone genes in a mouse model of enhanced S-cone syndrome.
A hybrid photoreceptor expressing both rod and cone genes in a mouse model of enhanced S-cone syndrome.
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在增强型 S 锥体综合征小鼠模型中表达视杆细胞和视锥细胞基因的混合光感受器。
DOI：
10.1371/journal.pgen.0010011
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发表时间：
2005-08
期刊：
影响因子：
4.5
通讯作者：
Cepko, CL
中科院分区：
文献类型：
--
作者：
Corbo, JC;Cepko, CL
视杆和视锥光感受器分别在昏暗和明亮的光条件下维持视觉。它们功能上的差异被认为是源于它们不同的基因表达模式、形态和突触连接。在这项研究中，我们已经检查了视网膜变性7（rd 7）突变小鼠，为人类增强的S-锥综合征（ESCS）的模型的感光细胞。该突变体在小鼠NR 2 E3的直系同源物中携带自发缺失，NR 2 E3是ESCS中突变的孤儿核受体转录因子。采用微阵列和原位杂交分析，我们已经发现，rd 7视网膜包含适度增加的S-视蛋白表达细胞，超微结构上似乎是正常的锥细胞。引人注目的是，rd 7视网膜中的大多数光感受器代表了一种表达视杆细胞和视锥细胞特异性基因的形态学杂交细胞类型。此外，在原位杂交筛选的基因显示上调的rd 7突变视网膜微阵列确定了10个新的锥特异性或锥富集的基因，具有广泛的生化功能，包括两个基因，特别是参与葡萄糖/糖原代谢。我们认为ESCS患者的异常视网膜电图、缓慢的视网膜变性和视网膜形态异常可能部分归因于与本研究中鉴定的类似的混合型感光细胞类型的异常功能。这里确定的新的视锥细胞特异性基因的功能多样性表明杆细胞和视锥细胞之间的分子差异远远超出了以前发现的。视觉始于光线进入眼睛。光线投射到视网膜上，视网膜是一种排列在眼睛内部的薄神经结构。光感受器是视网膜中最重要的细胞类型之一，是第一个接收入射光线的细胞。在哺乳动物中，有两种类型的光感受器：杆和锥。视杆细胞专门用于夜间视觉，视锥细胞专门用于白天和彩色视觉。在这项研究中，作者检查了一只基因突变导致感光细胞异常发育的小鼠的感光细胞。具有类似突变的人类有一种称为增强型S-视锥综合征（ESCS）的失明形式。令人惊讶的是，发现这种突变小鼠中的大多数光感受器具有正常视杆细胞和视锥细胞的特征。这些光感受器的异常特征可能使它们易于过早死亡。如果这个模型准确地反映了患有ESCS的人类患者的情况，它可能会为这种疾病中看到的视力丧失提供解释。这项研究还阐明了以前未知的正常杆和锥细胞之间的分子差异。这些新知识可能有助于更好地全面了解夜间，白天和色觉的机制。
Rod and cone photoreceptors subserve vision under dim and bright light conditions, respectively. The differences in their function are thought to stem from their different gene expression patterns, morphologies, and synaptic connectivities. In this study, we have examined the photoreceptor cells of the retinal degeneration 7 (rd7) mutant mouse, a model for the human enhanced S-cone syndrome (ESCS). This mutant carries a spontaneous deletion in the mouse ortholog of NR2E3, an orphan nuclear receptor transcription factor mutated in ESCS. Employing microarray and in situ hybridization analysis we have found that the rd7 retina contains a modestly increased number of S-opsin–expressing cells that ultrastructurally appear to be normal cones. Strikingly, the majority of the photoreceptors in the rd7 retina represent a morphologically hybrid cell type that expresses both rod- and cone-specific genes. In addition, in situ hybridization screening of genes shown to be up-regulated in the rd7 mutant retina by microarray identified ten new cone-specific or cone-enriched genes with a wide range of biochemical functions, including two genes specifically involved in glucose/glycogen metabolism. We suggest that the abnormal electroretinograms, slow retinal degeneration, and retinal dysmorphology seen in humans with ESCS may, in part, be attributable to the aberrant function of a hybrid photoreceptor cell type similar to that identified in this study. The functional diversity of the novel cone-specific genes identified here indicates molecular differences between rods and cones extending far beyond those previously discovered. Vision begins with light entering the eye. This light is projected onto the retina, a thin neural structure lining the inside of the eye. Photoreceptors, among the most important cell types in the retina, are the first to receive the incoming rays of light. In mammals, there are two types of photoreceptors: rods and cones. Rods are specialized for nighttime vision, and cones for daytime and color vision. In this study, the authors examined the photoreceptors of a mouse with a gene mutation that causes photoreceptors to develop abnormally. Humans with a similar mutation have a form of blindness called enhanced S-cone syndrome (ESCS). Surprisingly, the majority of photoreceptors in this mutant mouse were found to have features of both normal rods and cones. It is possible that the abnormal features of these photoreceptors predispose them to undergo premature death. If this model accurately reflects the situation in human patients with ESCS, it may provide an explanation for the loss of vision seen in this disease. This study also elucidated previously unknown molecular differences between normal rods and cones. This new knowledge may contribute to a better overall understanding of the mechanisms underlying night, day, and color vision.
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