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.