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Our previous large\u2010scale genome\u2010wide association study demonstrated that the African G6PD deficient A\u2010 variant (rs1050828, Val68Met) is associated with higher oxidative hemolysis after cold storage. Despite a high prevalence of X\u2010linked G6PD mutation in African American population (>10%), blood donors are not routinely screened for G6PD status and its importance in transfusion medicine is relatively understudied.<\/jats:p><\/jats:sec>Study Design and Methods<\/jats:title>To further evaluate the functional effects of the G6PD A\u2010 mutation, we created a novel mouse model carrying this genetic variant using CRISPR\u2010Cas9. We hypothesize that this humanized G6PD A\u2010 variant is associated with reduced G6PD activity with a consequent effect on RBC hemolytic propensity and post\u2010transfusion recovery.<\/jats:p><\/jats:sec>Results<\/jats:title>G6PD A\u2010 RBCs had reduced G6PD protein with ~5% residual enzymatic activity. Significantly increased in vitro<\/jats:italic> hemolysis induced by oxidative stressors was observed in fresh and stored G6PD A\u2010 RBCs, along with a lower GSH:GSSG ratio. However, no differences were observed in storage hemolysis, osmotic fragility, mechanical fragility, reticulocytes, and post\u2010transfusion recovery. Interestingly, a 14% reduction of 24\u2010h survival following irradiation was observed in G6PD A\u2010 RBCs compared to WT RBCs. Metabolomic assessment of stored G6PD A\u2010 RBCs revealed an impaired pentose phosphate pathway (PPP) with increased glycolytic flux, decreasing cellular antioxidant capacity.<\/jats:p><\/jats:sec>Discussion<\/jats:title>This novel mouse model of the common G6PD A\u2010 variant has impaired antioxidant capacity like humans and low G6PD activity may reduce survival of transfused RBCs when irradiation is performed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/trf.17756","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T07:49:24Z","timestamp":1708760964000},"page":"615-626","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Functional effects of an African glucose\u20106\u2010phosphate dehydrogenase (G6PD) polymorphism (Val68Met<\/scp>) on red blood cell<\/scp> hemolytic propensity and post\u2010transfusion recovery"],"prefix":"10.1111","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4333-3158","authenticated-orcid":false,"given":"Ling","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedics and Rehabilitation University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth R.","family":"Rochon","sequence":"additional","affiliation":[{"name":"University of Maryland School of Medicine University of Maryland Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastien","family":"Gingras","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin E.","family":"Zuchelkowski","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine University of Pittsburgh Medical Center Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Sinchar","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine University of Pittsburgh Medical Center Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elimira","family":"Alipour","sequence":"additional","affiliation":[{"name":"Department of Physics Wake Forest University Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Reisz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minying","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, 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