Expression of human alpha-globin and mouse/human hybrid beta-globin genes in murine hemopoietic stem cells transduced by recombinant retroviruses.

Murine cell lines releasing helper-free recombinant retroviruses containing human alpha-globin and mouse/human hybrid beta-globin genes were generated. The expression of the hybrid beta-globin gene but not the human alpha-globin gene was regulated appropriately in infected mouse erythroid leukemia (MEL) cells. Murine bone marrow cells were infected by coculture with virus-producing cells and transplanted into lethally irradiated syngeneic recipients. Greater than 90% of the spleen colonies (12-15 days), which are derived from hemopoietic multipotential stem cells, showed proviral integration. Various levels of expression of the transduced globin genes were detected in all of the provirus-positive spleen colonies. Proviral sequences and transcripts from the transduced globin genes could also be detected in a few long-term reconstituted recipients in an observation period of 10 months after transplantation. IMAGES: