Synthesis of functional human hemoglobin in transgenic mice.
Synthesis of functional human hemoglobin in transgenic mice.
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转基因小鼠中功能性人血红蛋白的合成。
DOI：
10.1126/science.2772649
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Townes,TM
中科院分区：
文献类型：
--
作者：
Behringer,RR;Ryan,TM;Reilly,MP;Asakura,T;Palmiter,RD;Brinster,RL;Townes,TM
人α-和β-珠蛋白基因分别融合在两个红系特异性脱氧核糖核酸酶(DNA Ase)I超敏感部位的下游，这两个超敏感部位通常位于人β-珠蛋白基因上游50kb。这两个构建物被共同注射到受精卵中，并在发育的转基因动物中进行了表达分析。拥有完整转基因拷贝的小鼠在红系组织中表达了高水平的正确启动的人类α和β珠蛋白信使核糖核酸。在成人红细胞中形成了一种真正的人血红蛋白，纯化后的氧平衡曲线与天然人血红蛋白A(HbA)的曲线相同。因此，可以在转基因小鼠中合成具有功能的人血红蛋白。这为生产镰状细胞病等人类血红蛋白疾病的小鼠模型提供了基础。
Human α- and β-globin genes were separately fused downstream of two erythroid-specific deoxyribonuclease (DNase) I super-hypersensitive sites that are normally located 50 kilobases upstream of the human β-globin gene. These two constructs were coinjected into fertilized mouse eggs, and expression was analyzed in transgenic animals that developed. Mice that had intact copies of the transgenes expressed high levels of correctly initiated human α- and β-globin messenger RNA specifically in erythroid tissue. An authentic human hemoglobin was formed in adult erythrocytes that when purified had an oxygen equilibrium curve identical to the curve of native human hemoglobin A (Hb A). Thus, functional human hemoglobin can be synthesized in transgenic mice. This provides a foundation for production of mouse models of human hemoglobinopathies such as sickle cell disease.