Understanding the relevance of hemoglobin in RPE

本研究将产生人源化RPE特异性珠蛋白基因敲除小鼠，以阐明 视网膜色素上皮（RPE）细胞中的血红蛋白。视网膜色素上皮细胞有许多功能， 维持外部视网膜健康和整体视觉功能。其中最新发现的是 血红蛋白的产生，这种现象一度被认为是专属于红细胞谱系的细胞。 我们假设RPE-血红蛋白对于维持RPE和视网膜形态是重要的， 视觉功能以及维持外层视网膜中的氧稳态。我们之前的研究 证实了RPE产生血红蛋白，然而RPE产生的血红蛋白的功能意义 血红蛋白尚未得到证实。没有可用的活动物模型，可以用于研究 非红系（RPE）产生的血红蛋白，独立于红系细胞产生的血红蛋白。拟议 研究试图开发一个。具体来说，我们将产生一个人源化的条件珠蛋白基因敲除 小鼠，在除RPE之外的所有血红蛋白表达细胞类型中表达人血红蛋白的模型。的 在该模型中，RPE中缺乏血红蛋白的结果将提供关于以下方面的宝贵信息： 正常情况下RPE-血红蛋白的功能。此外，新的动物模型是 产生的人源化条件性血红蛋白敲除小鼠，将随时提供给更广泛的 研究社区作为一种工具来研究血红蛋白的细胞类型的具体意义。

This study will generate a humanized RPE-specific globin gene knockout mouse to elucidate the function of hemoglobin in retinal pigment epithelial (RPE) cells. RPE cells serve many functions essential to the maintenance of outer retinal health and overall visual function. Newly discovered among these, is the production of hemoglobin, a phenomenon once thought to be reserved exclusively for cells of erythroid lineage. We hypothesize that RPE-hemoglobin is important for the maintenance of RPE and retinal morphology and visual function in addition to maintenance of oxygen homeostasis in outer retina. Our prior studies have confirmed the production of hemoglobin by RPE, however the functional significance of RPE-generated hemoglobin has not been demonstrated. There is no live animal model available that allows for the study of non-erythroid (RPE)-generated hemoglobin independent of that generated by erythroid cells. The proposed study seeks to develop one. Specifically, we will generate a humanized conditional globin gene knockout mouse, a model that expresses human hemoglobin in all hemoglobin-expressing cell types except RPE. The consequences of the absence of hemoglobin in RPE in this model will provide invaluable information regarding the function of RPE-hemoglobin under normal conditions. Additionally, the novel animal model to be generated, a humanized conditional hemoglobin knockout mouse, will be made readily available to the broader research community as a tool to study the cell-type specific significance of hemoglobin.