title: Human fetal-to-adult globin gene switching in transgenic mice: persistent expression of the G gamma-globin gene in the Japanese HPFH.
abstract: 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.
authors.affiliation: Research Laboratory for Genetic Information, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Katsube
authors.forename: H
authors.initials: H
authors.lastname: Tojo
authors.forename: T
authors.initials: T
authors.lastname: Sakaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Fukumaki
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D004622:Embryo, Mammalian; D005314:Embryonic and Fetal Development; D005319:Fetal Hemoglobin / Q000235:genetics*; D005333:Fetus; D015870:Gene Expression; D005914:Globins / Q000235:genetics*; D006441:Hemoglobin A / Q000235:genetics*; D006453:Hemoglobinopathies / Q000097:blood / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007564:Japan; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015183:Restriction Mapping
chemical_list: D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D005914:Globins; D006441:Hemoglobin A; D005319:Fetal Hemoglobin