Ryan T M, Townes T M, Reilly M P, Asakura T, Palmiter R D, Brinster R L, Behringer R R
Department of Biochemistry, School of Medicine, University of Alabama, Birmingham 35294.
Science. 1990 Feb 2;247(4942):566-8. doi: 10.1126/science.2154033.
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.
将含有插入到红系特异性脱氧核糖核酸酶I超敏感位点下游的人类α和βs-珠蛋白基因的DNA分子共注射到受精的小鼠卵中，并建立了一个合成人类镰状血红蛋白（Hb S）的转基因小鼠品系。将这些动物与β地中海贫血小鼠杂交以降低内源性小鼠珠蛋白水平。当这些小鼠的红细胞脱氧时，超过90%的细胞呈现出与镰状细胞病患者红细胞相同的特征性镰状形态。与对照组相比，这些小鼠的血细胞比容降低、网织红细胞计数升高、血红蛋白浓度降低以及脾肿大，这些都是与人类镰状细胞病相关的贫血的迹象。
