Ablation of Chop Transiently Enhances Photoreceptor Survival but Does Not Prevent Retinal Degeneration in Transgenic Mice Expressing Human P23H Rhodopsin
Ablation of Chop Transiently Enhances Photoreceptor Survival but Does Not Prevent Retinal Degeneration in Transgenic Mice Expressing Human P23H Rhodopsin
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DOI：
10.1007/978-3-319-17121-0_25
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发表时间：
2016-01-01
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影响因子：
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通讯作者：
Lin, Jonathan H.
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文献类型：
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作者：
Chiang, Wei-Chieh;Joseph, Victory;Lin, Jonathan H.
RHO（视杆蛋白）编码G蛋白偶联受体，其仅由视网膜的视杆光感受器表达，并且当与11-顺式-视黄醛偶联时形成必需的色素视紫红质。许多视杆蛋白疾病-突变导致视杆蛋白错误折叠并触发内质网（ER）应激，导致未折叠蛋白反应（UPR）信号转导网络的激活。Chop是一种由ER应激诱导的转录激活因子，并促进细胞对慢性ER应激的反应。在这里，我们研究了Chop在经历视网膜变性的表达人P23 H视紫红质（hP 23 H Rho Tg）的转基因小鼠中的作用。除了一个时间点之外，我们发现在这些动物中没有显著的Chop诱导，并且当hP 23 H Rho Tg动物被饲养到Chop（-/-）背景中时，通过组织学和电生理学，视网膜变性没有显著变化。我们的研究结果表明，在这些动物的视网膜变性过程中，Chop并没有发挥重要的因果作用。我们认为，ER应激诱导的UPR信号网络的其他模块可能参与P23 H视紫红质诱导的感光细胞疾病。
RHO (Rod opsin) encodes a G-protein coupled receptor that is expressed exclusively by rod photoreceptors of the retina and forms the essential photopigment, rhodopsin, when coupled with 11-cis-retinal. Many rod opsin disease -mutations cause rod opsin protein misfolding and trigger endoplasmic reticulum (ER) stress, leading to activation of the Unfolded Protein Response (UPR) signal transduction network. Chop is a transcriptional activator that is induced by ER stress and promotes cell death in response to chronic ER stress. Here, we examined the role of Chop in transgenic mice expressing human P23H rhodopsin (hP23H Rho Tg) that undergo retinal degeneration. With the exception of one time point, we found no significant induction of Chop in these animals and no significant change in retinal degeneration by histology and electrophysiology when hP23H Rho Tg animals were bred into a Chop(-/-) background. Our results indicate that Chop does not play a significant causal role during retinal degeneration in these animals. We suggest that other modules of the ER stress-induced UPR signaling network may be involved photoreceptor disease induced by P23H rhodopsin.