βMinor-globin messenger RNA accumulation in reticulocytes governs improved erythropoiesis in β thalassemic mice after erythropoietin complementary DNA electrotransfer in muscles

摘要: Mechanisms governing the induction of effective erythropoiesis in response to erythropoietin (Epo) oversecretion have been investigated beta thalassemic C57Bl/6(Hbbth) mice. Naked DNA encoding an expression vector for mouse Epo was introduced into skeletal muscles by electrotransfer. A transient increase serum concentrations with a proportional augmentation hematocrit values observed. Various parameters relevant thalassemia were surveyed blood samples taken before treatment, at peak secretion, and when phenotype reverted anemia. We measured globin messenger RNA (mRNA) levels reticulocytes real-time quantitative polymerase chain reaction, synthesis levels, several indicators erythrocyte membrane quality, including bound alpha chains, immunoglobulins, main protein components, iron compartmentalization. Data indicated that high primarily affect betaminor-globin mRNA accumulation reticulocytes. Other changes subsequent intense stimulation, like increased betaminor/alpha-globin ratio, reduced chains immunoglobulins membranes, improved spectrin/band 3 red cell survival, appeared as consequences levels. This conclusion is consistent models postulating stimulation induces expansion differentiation erythroid progenitors committed fetal erythropoiesis. Although phenotypic correction partial mice, comparable achievements will probably be more difficult obtain humans, naked electrotransfer may provide safe low-cost method reassessing potentials inducer reactivation patients thalassemia.