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Science 2 February 1990:
Vol. 247. no. 4942, pp. 566 - 568
DOI: 10.1126/science.2154033
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Articles

Science, Vol 247, Issue 4942, 566-568
Copyright © 1990 by American Association for the Advancement of Science

articles

Human sickle hemoglobin in transgenic mice

TM Ryan, TM Townes, MP Reilly, T Asakura, RD Palmiter, RL Brinster, and RR Behringer

Department of Biochemistry, School of Medicine, University of Alabama, Birmingham 35294.

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.


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