Session: 113. Hemoglobinopathies, Excluding Thalassemia: Basic and Translational: Poster III
Hematology Disease Topics & Pathways:
Research, Sickle Cell Disease, Translational Research, Hemoglobinopathies, Diseases, Technology and Procedures, gene editing
Blood from three sickle cell edited lambs (SCEL) and age-matched controls (AMC) were evaluated by the same diagnostic methods used in humans: hematocrit, blood smears, reticulocyte counts, alkaline and capillary hemoglobin (Hb) electrophoresis, Hb solubility tests, and ektacytometry. Peripheral blood (PB) smears in SCEL exhibit sickled erythrocytes, acanthocytes, target cells, normoblasts, and polychromasia, while AMC displayed normal PB smears. Reticulocyte counts via flow cytometry were slightly elevated in SCEL when compared to AMC. All 3 SCEL displayed positive SickleDex tests at birth and at all time points analyzed thereafter – these tests were consistently negative in AMC. Alkaline and capillary Hb electrophoresis demonstrated the presence of an abnormal Hb with the same migration pattern as the human HbS, and the presence of HbF at birth. HbF waned progressively to disappear by 3 months, being replaced by HbS in SCEL and normal adult Hb in AMC. In addition, ektacytometry demonstrated a leftward shift of the elongation index–osmolality curves. These data indicate that introduction of the human SCD mutation in the sheep β-globin gene results in a similar phenotype at the blood level, thereby potentially producing a similar disease phenotype and progression in the sheep model. Our findings thus support the translational relevance of the SCD sheep model and highlight the potential for its future use in the development of novel therapies for SCD.
Disclosures: Kim-Shapiro: Beverage Operations, LLC: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: co-inventor on a patent related to the use of nitrite under cardiovascular conditions, and a co-author on patents related to treatment of hemolysis.
See more of: Oral and Poster Abstracts