Human Fetal-to-Adult Globin Gene Switching in Transgenic Mice: Persistent Expression of the Gγ-Globin Gene in the Japanese HPFH

Abstract

We linked a 3.3 kb fragment containing the human γ-globin gene together with a 5.5 kb fragment containing the human β-globin gene. This construct was introduced into the germ line of mice. Analysis of the resulting transgenic mice showed that expression of the human γ- and β-globin genes were regulated as that of the mouse embryonic and adult globin genes and human γ-to-β globin switching was reconstructed in the mice. By replacing the γ-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 β-globin gene expression is regulated. In this system expression of the Gγ-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 β-globin expression in fetal and adult mice.