Long-term expression of the human beta-globin gene after retroviral transfer into pluripotent hematopoietic stem cells of the mouse

Advances in Experimental Medicine and Biology
R GelinasU Novak

Abstract

We have studied the regulation of the human beta-globin gene after retroviral transfer into a variety of transformed and normal hematopoietic cells. After transfer into murine erythroleukemia cells (MEL) expression from the human beta-globin gene responds to inducers of erythroid maturation in parallel to the endogenous murine globin genes. After infection of human BFU-E, RNA expression from the virally-transferred beta-globin gene was measured at 2.5%-5% of the endogenous beta-globin level. The most improved globin vectors can transfer the human beta-globin gene into pluripotent hematopoietic stem cells in mouse bone marrow. Mice reconstituted with infected marrow show human beta-globin RNA and protein expression in peripheral blood cells for over 4 months. In these animals, both myeloid and lymphoid cells carry the integrated provirus at a level of about 1 copy per cell. In serial transplantation experiments, bone marrow from these animals is capable of repopulating secondary and tertiary recipient animals which go on to show long-term human beta-globin expression. Retroviral vectors thus provide a practical way to refine models of globin gene regulation through in vivo tests and to evaluate the feasibility of protocols for g...Continue Reading

Citations

May 31, 1994·Annals of the New York Academy of Sciences·M K BrennerJ N Ihle
Dec 1, 1995·Journal of Hematotherapy·G D Schmidt-Wolf, I G Schmidt-Wolf
Jul 19, 2013·The Journal of Clinical Investigation·Zulema RomeroDonald B Kohn
Jan 1, 1993·Cancer Investigation·S M Freeman, J A Zwiebel

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