title: Inactivation of mouse alpha-globin gene by homologous recombination: mouse model of hemoglobin H disease.
abstract: We have disrupted the 5' locus of the duplicated adult alpha-globin genes by gene targeting in the mouse embryonic stem cells and created mice with alpha-thalassemia syndromes. The heterozygous knockout mice (.alpha/alpha alpha) are asymptomatic like the silent carriers in humans whereas the homozygous knockout mice (.alpha/.alpha) show hemolytic anemia. Mice with three dysfunctional alpha-globin genes generated by breeding the 5' alpha-globin knockouts (.alpha/alpha alpha) and the deletion type alpha-thalassemia mice (../alpha alpha) produce severe hemoglobin H disease and they die in utero. These results indicate that the 5' alpha-globin gene is the predominant locus in mice, and suggest that it is even more dominant than its human homologue.
authors.affiliation: Department of Laboratory Medicine, Howard Hughes Medical Institute, University of California, San Francisco 94143-0724, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: R H
authors.initials: RH
authors.lastname: Lu
authors.forename: S M
authors.initials: SM
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Meneses
authors.forename: K
authors.initials: K
authors.lastname: Chan
authors.forename: R
authors.initials: R
authors.lastname: Pedersen
authors.forename: Y W
authors.initials: YW
authors.lastname: Kan
mesh_terms: D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology; D005313:Fetal Death / Q000235:genetics; D018390:Gene Targeting; D005799:Genes, Dominant; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006801:Humans; D051379:Mice / Q000196:embryology / Q000235:genetics*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family; D011995:Recombination, Genetic; D017384:Sequence Deletion; D013234:Stem Cells; D017085:alpha-Thalassemia / Q000196:embryology / Q000235:genetics*
chemical_list: D005914:Globins