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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Samakoglu, S. Articles by Bohl, D. Search for Related Content PubMed PubMed Citation Articles by Samakoglu, S. Articles by Bohl, D. Related Collections Red Cells Gene Expression Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2001, Vol. 97, No. 8, pp. 2213-2220 GENE THERAPY Minor-globin messenger RNA accumulation in reticulocytes governs improved erythropoiesis in  thalassemic mice after erythropoietin complementary DNA electrotransfer in muscles Selda Samakoglu, Elena Fattori, Stefania Lamartina, Carlo Toniatti, Daniel Stockholm, Jean Michel Heard, and Delphine Bohl From Laboratoire Rétrovirus et Transfert Génétique, CNRS URA 1930; Institut Pasteur, Paris, France; IRBM, Pomezia, Italy; and Généthon III, CNRS URA1923, Evry, France. Mechanisms governing the induction of effective erythropoiesis in response to erythropoietin (Epo) oversecretion have been investigated in  thalassemic C57Bl/6Hbbth mice. Naked DNA encoding an expression vector for mouse Epo was introduced into skeletal muscles by electrotransfer. A transient increase of serum Epo concentrations with a proportional augmentation of hematocrit values was observed. Various parameters relevant to  thalassemia were surveyed in blood samples taken before treatment, at the peak of Epo secretion, and when the phenotype reverted to anemia. We measured globin messenger RNA (mRNA) levels in reticulocytes by real-time quantitative polymerase chain reaction, globin chain synthesis levels, and several indicators of erythrocyte membrane quality, including bound  chains, bound immunoglobulins, main protein components, and iron compartmentalization. Data indicated that high serum Epo levels primarily affect minor-globin mRNA accumulation in reticulocytes. Other changes subsequent to intense Epo stimulation, like increased minor/-globin chain synthesis ratio, reduced levels of  chains and immunoglobulins bound to membranes, improved spectrin/band 3 ratio, increased red blood cell survival, and improved erythropoiesis appeared as consequences of increased minor-globin mRNA levels. This conclusion is consistent with models postulating that intense Epo stimulation induces the expansion and differentiation of erythroid progenitors committed to fetal erythropoiesis. Although phenotypic correction was partial in mice, and comparable achievements will probably be more difficult to obtain in humans, naked DNA electrotransfer may provide a safe and low-cost method for reassessing the potentials of Epo as an inducer of fetal erythropoiesis reactivation in patients with  thalassemia. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Song, J. Luo, W. Luo, J. Weng, Z. Wang, B. Li, D. Li, and M. Liu Inactivation of G-protein-coupled Receptor 48 (Gpr48/Lgr4) Impairs Definitive Erythropoiesis at Midgestation through Down-regulation of the ATF4 Signaling Pathway J. Biol. Chem., December 26, 2008; 283(52): 36687 - 36697. [Abstract] [Full Text] [PDF] D. A. Dean Nonviral gene transfer to skeletal, smooth, and cardiac muscle in living animals Am J Physiol Cell Physiol, August 1, 2005; 289(2): C233 - C245. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020