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

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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.