Expression of human beta-globin genes in transgenic mice: effects of a flanking metallothionein-human growth hormone fusion gene.
In an attempt to place a human beta-globin gene in an open chromatin domain regardless of its site of integration in the mouse genome, we microinjected into fertilized mouse eggs a construct in which the human beta-globin gene and a mouse metallothionein-human growth hormone fusion gene were juxtaposed and oriented in opposite directions. Mice that developed from injected eggs and that grew larger than normal were analyzed for human beta-globin mRNA. The globin genes were not expressed in erythroid tissue but were expressed with the same tissue specificity as metallothionein-human growth hormone. These results suggest that sequences which control metallothionein-human growth hormone gene expression are capable of stimulating the expression of a flanking gene in an orientation-independent and tissue-specific manner. As a control for this experiment, we deleted the metallothionein-human growth hormone transcription unit and noted that the human beta-globin gene then was expressed at high levels with erythroid tissue specificity.
D000818:Animals; D004262:DNA Restriction Enzymes; D004720:Endonucleases; D005796:Genes; D005914:Globins / Q000235:genetics*; D013006:Growth Hormone / Q000235:genetics*; D006801:Humans; D008668:Metallothionein / Q000235:genetics*; D051379:Mice; D008845:Microinjections; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014018:Tissue Distribution; D014158:Transcription, Genetic
D012333:RNA, Messenger; D013006:Growth Hormone; D005914:Globins; D008668:Metallothionein; D004720:Endonucleases; D004262:DNA Restriction Enzymes; D015719:Single-Strand Specific DNA and RNA Endonucleases