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.
Li
C L
CL
Molecular Biology and Virology Laboratory, Salk Institute, San Diego, CA 92138.
Dwarki
V J
VJ
Verma
I M
IM
D000818:Animals; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D015870:Gene Expression; D005796:Genes; D005822:Genetic Vectors; D005914:Globins / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D012190:Retroviridae / Q000235:genetics*; D013154:Spleen / Q000166:cytology; D013997:Time Factors
D012333:RNA, Messenger; D005914:Globins