title: Human sickle hemoglobin in transgenic mice.
abstract: DNA molecules that contain the human alpha- and beta s-globin genes inserted downstream of erythroid-specific, deoxyribonuclease I super-hypersensitive sites were coinjected into fertilized mouse eggs and a transgenic mouse line was established that synthesizes human sickle hemoglobin (Hb S). These animals were bred to beta-thalassemic mice to reduce endogenous mouse globin levels. When erythrocytes from these mice were deoxygenated, greater than 90 percent of the cells displayed the same characteristic sickled shapes as erythrocytes from humans with sickle cell disease. Compared to controls the mice have decreased hematocrits, elevated reticulocyte counts, lower hemoglobin concentrations, and splenomegaly, which are all indications of the anemia associated with human sickle cell disease.
authors.affiliation: Department of Biochemistry, School of Medicine, University of Alabama, Birmingham 35294.
authors.forename: T M
authors.initials: TM
authors.lastname: Ryan
authors.forename: T M
authors.initials: TM
authors.lastname: Townes
authors.forename: M P
authors.initials: MP
authors.lastname: Reilly
authors.forename: T
authors.initials: T
authors.lastname: Asakura
authors.forename: R D
authors.initials: RD
authors.lastname: Palmiter
authors.forename: R L
authors.initials: RL
authors.lastname: Brinster
authors.forename: R R
authors.initials: RR
authors.lastname: Behringer
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood / Q000235:genetics; D000818:Animals; D004247:DNA / Q000235:genetics; D004251:DNA Transposable Elements; D004912:Erythrocytes / Q000648:ultrastructure; D005796:Genes; D005914:Globins / Q000235:genetics*; D006451:Hemoglobin, Sickle / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning
chemical_list: D004251:DNA Transposable Elements; D006451:Hemoglobin, Sickle; D005914:Globins; D004247:DNA