Understanding the relevance of hemoglobin in RPE

本研究将产生人源化的RPE特异性珠蛋白基因敲除小鼠，以阐明其功能 视网膜色素上皮(RPE)细胞的血红蛋白。RPE细胞具有许多必需的功能， 维护外部视网膜健康和整体视觉功能。其中最新发现的是 产生血红蛋白，这一现象曾被认为是红系细胞特有的现象。 我们假设RPE-Hb对维持RPE和视网膜形态和 除了维持外部视网膜的氧平衡外，还有视觉功能。我们之前的研究已经 证实了RPE产生血红蛋白，但RPE产生的功能意义 血红蛋白还没有被证实。目前还没有活体动物模型可以用来研究 非红系(RPE)产生的独立于红系细胞产生的血红蛋白。建议数 研究试图开发出一种。具体地说，我们将产生人源化的条件性珠蛋白基因敲除 小鼠，一种在除RPE以外的所有表达血红蛋白的细胞类型中表达人血红蛋白的模型。这个 在这个模型中，RPE中没有血红蛋白的后果将提供关于 正常情况下RPE-血红蛋白的功能。此外，新的动物模型将是 一种人源化的条件性血红蛋白基因敲除小鼠，将随时提供给更广泛的人 研究界以此为工具研究细胞类型对血红蛋白的具体意义。

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.