COMPARATIVE PROFILING OF RED BLOOD CELLS FROM THE BETA-ADDUCIN KNOCKOUT MOUSE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 遗传性溶血性贫血（球形红细胞增多症或椭圆形红细胞增多症）是最常见的遗传性疾病之一。 虽然轻度至重度的遗传性溶血性贫血可由红细胞（RBC）膜骨架缺陷引起，但围绕已知红细胞突变的临床变异性的基本问题仍未得到解答。 为了鉴定涉及溶血性贫血病理生理学的候选蛋白，我们利用无标记比较方法来检测来自正常小鼠和β-内收蛋白敲除小鼠的RBC的差异。 我们鉴定了在这些样品之间具有不同丰度的>600 μ LC-MS区域。 在检测到的差异区域中，仅~16%被映射到MS/MS肽鉴定。 我们在β-内收蛋白敲除RBC中检测到6种蛋白质减少，48种蛋白质丰度更高。 虽然蛋白质差异跨越广泛的细胞过程，但一些蛋白质是疾病严重程度修饰剂的有吸引力的候选者。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Inherited hemolytic anemia (spherocytosis or elliptocytosis) is one of the most common inherited diseases. While mild to severe inherited hemolytic anemias can arise from defects in the red blood cell (RBC) membrane skeleton, fundamental questions remain unanswered surrounding the clinical variability of known red blood cell mutations. To identify candidate proteins involved hemolytic anemia pathophysiology, we utilized a label-free comparative approach to detect differences in RBCs from normal mice and beta-adducin knock-out mice. We identified >600 uLC-MS regions that have a different abundance between these samples. Of the detected difference regions, only ~16% were mapped to MS/MS peptide identifications. We detected 6 proteins that were decreased and 48 proteins with a greater abundance in the beta-adducin knock-out RBC. While the protein differences span a broad range of cellular processes, some of the proteins are attractive candidates for modifiers of disease severity.