Human α-Globin Genes Demonstrate Autonomous Developmental Regulation in Transgenic Mice

Abstract

Recent studies have demonstrated that transcriptional activation of the human adult β-globin transgene in mice by coinsertion of the β-globin cluster locus control region (β-LCR) results in loss of its adult restricted pattern of expression. Normal developmental control is reestablished by coinsertion of the fetal γ-globin transgene in cis to the adult β-globin gene. To test the generality of this interdependence of two globin genes for their proper developmental control, we generated transgenic mice in which the human adult α-globin genes are transcriptionally activated by the β-LCR either alone or in cis to their corresponding embryonic ζ-globin gene. In both cases, the human globin transgenes were expressed at the appropriate developmental period. In contrast to the β-globin gene, developmental control of the human adult α-globin transgenes appears to be autonomous and maintained even when activated by an adjacent locus control region.