Human fetal-to-adult globin gene switching in transgenic mice: persistent expression of the G gamma-globin gene in the Japanese HPFH.

We linked a 3.3 kb fragment containing the human gamma-globin gene together with a 5.5 kb fragment containing the human beta-globin gene. This construct was introduced into the germ line of mice. Analysis of the resulting transgenic mice showed that expression of the human gamma- and beta-globin genes were regulated as that of the mouse embryonic and adult globin genes and human gamma-to-beta globin switching was reconstructed in the mice. By replacing the gamma-globin gene in the construct with modified counterparts, this transgenic mouse system enables us to analyze cis-acting elements essential for erythroid-specific and developmental stage-specific expression of the test gene under the condition in which human beta-globin gene expression is regulated. In this system expression of the G gamma-globin gene bearing the point mutation found in a Japanese patient of hereditary persistence of fetal hemoglobin (HPFH) (1) persisted at a equivalent level to beta-globin expression in fetal and adult mice.