Human Sickle Hemoglobin in Transgenic Mice

• Published in: Science (American Association for the Advancement of Science) Vol. 247; no. 4942; pp. 566 - 568
• Main Authors: Ryan, Thomas M., Townes, Tim M., Reilly, Michael P., Asakura, Toshio, Palmiter, Richard D., Brinster, Ralph L., Behringer, Richard R.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 02.02.1990; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Anemia, Sickle Cell - blood; Anemia, Sickle Cell - genetics; Anemias. Hemoglobinopathies; Animals; Biological and medical sciences; Blood; Disease; Diseases of red blood cells; DNA - genetics; DNA Transposable Elements; Erythrocyte disorders; Erythrocytes; Erythrocytes - ultrastructure; Genes; Genetic aspects; Genetic disorders; globin; Globin genes; Globins - genetics; Hematologic and hematopoietic diseases; Hemoglobin, Sickle - genetics; Hemoglobin, Sickle - isolation & purification; Hemoglobins; House mouse; Humans; Infections; Medical sciences; Messenger RNA; Mice; Mice as laboratory animals; Mice, Transgenic; Microscopy, Electron; Microscopy, Electron, Scanning; Reticulocytes; RNA; Sickle cell anemia; Sickle cell disease; Sickles; Transgenic animals; Hemoglobinopathy; Vertebrata; Experimental disease; Mammalia; Sickle cell anemia; Mouse; Animal; Rodentia; Transgenic animal; Hemopathy
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2154033

DNA molecules that contain the human α- 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 β-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.