title: A dual reporter mouse model of the human β-globin locus: applications and limitations.
abstract: The human β-globin locus contains the β-like globin genes (i.e. fetal γ-globin and adult β-globin), which heterotetramerize with α-globin subunits to form fetal or adult hemoglobin. Thalassemia is one of the commonest inherited disorders in the world, which results in quantitative defects of the globins, based on a number of genome variations found in the globin gene clusters. Hereditary persistence of fetal hemoglobin (HPFH) also caused by similar types of genomic alterations can compensate for the loss of adult hemoglobin. Understanding the regulation of the human γ-globin gene expression is a challenge for the treatment of thalassemia. A mouse model that facilitates high-throughput assays would simplify such studies. We have generated a transgenic dual reporter mouse model by tagging the γ- and β-globin genes with GFP and DsRed fluorescent proteins respectively in the endogenous human β-globin locus. Erythroid cell lines derived from this mouse model were tested for their capacity to reactivate the γ-globin gene. Here, we discuss the applications and limitations of this fluorescent reporter model to study the genetic basis of red blood cell disorders and the potential use of such model systems in high-throughput screens for hemoglobinopathies therapeutics.
authors.affiliation: Department of Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Petros
authors.initials: P
authors.lastname: Papadopoulos
authors.forename: Laura
authors.initials: L
authors.lastname: Gutiérrez
authors.forename: Reinier
authors.initials: R
authors.lastname: van der Linden
authors.forename: John
authors.initials: J
authors.lastname: Kong-A-San
authors.forename: Alex
authors.initials: A
authors.lastname: Maas
authors.forename: Dubravka
authors.initials: D
authors.lastname: Drabek
authors.forename: George P
authors.initials: GP
authors.lastname: Patrinos
authors.forename: Sjaak
authors.initials: S
authors.lastname: Philipsen
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000166:cytology; D005319:Fetal Hemoglobin / Q000378:metabolism; D005456:Fluorescent Dyes / Q000494:pharmacology; D017930:Genes, Reporter; D016158:Genes, p53; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006453:Hemoglobinopathies / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D005810:Multigene Family; D055544:beta-Globins / Q000235:genetics*; D055545:gamma-Globins / Q000235:genetics*
chemical_list: D005456:Fluorescent Dyes; D055544:beta-Globins; D055545:gamma-Globins; D049452:Green Fluorescent Proteins; D005319:Fetal Hemoglobin