High-level erythroid expression of human alpha-globin genes in transgenic mice.
The human alpha 1-globin gene was fused downstream of two erythroid-specific DNase I super-hypersensitive sites that are normally located upstream of the human beta-globin locus. This construct was injected into fertilized mouse eggs, and expression was analyzed in 16-day fetal livers and brains. All 11 fetuses that contained intact copies of the transgene expressed correctly initiated human alpha-globin mRNA in the erythroid fetal liver but not in brain. Levels of expression ranged from 4% to 337% of endogenous mouse beta-globin mRNA. A human alpha-globin construct that did not contain super-hypersensitive sites was not expressed. These results demonstrate that human beta-globin locus activation sequences can stimulate high levels of human alpha-globin gene expression in erythroid tissue of transgenic mice. The results also provide a foundation for experiments designed to coexpress human alpha- and beta-globin genes in transgenic mice and suggest a feasible approach for production of a mouse model for human sickle cell disease.
Ryan
T M
TM
Department of Biochemistry, Schools of Medicine and Dentistry, University of Alabama, Birmingham 35294.
Behringer
R R
RR
Townes
T M
TM
Palmiter
R D
RD
Brinster
R L
RL
D000818:Animals; D015139:Blotting, Southern; D001921:Brain / Q000378:metabolism; D005333:Fetus; D005786:Gene Expression Regulation; D005796:Genes; D005914:Globins / Q000235:genetics*; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D005914:Globins