Hypoxia-induced in vivo sickling of transgenic mouse red cells.
Hypoxia-induced in vivo sickling of transgenic mouse red cells.
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缺氧诱导转基因小鼠红细胞体内镰状化。
DOI：
10.1172/jci115041
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Clift,SM
中科院分区：
文献类型：
--
作者：
Rubin,EM;Witkowska,HE;Spangler,E;Curtin,P;Lubin,BH;Mohandas,N;Clift,SM
为了开发镰状细胞性贫血的动物模型，我们创造了转基因小鼠，表达一种严重的自然发生的人类镰状血红蛋白，Hb S Antilles。由于其低溶解度和氧亲和力，Hb S Antilles比Hb S更容易引起红细胞镰状细胞坏死。为了制造表达高水平Hb S Antilles的转基因动物，来自人类β -珠蛋白簇的红细胞特异性DNAse I超敏位点II与人类α - 2-珠蛋白基因和β S Antilles基因独立连接。将两种构建体同时注入胚胎，获得7只转基因小鼠，其中3只同时含有人α和人β S安的列斯转基因。在将人类转基因基因与小鼠β -地中海贫血背景杂交后，获得了一种转基因小鼠系，其中小鼠红细胞中大约一半的β -珠蛋白链是人类β - S安的列斯。转基因红细胞体外脱氧导致广泛的镰状坏死。通过将这些转基因小鼠置于低氧环境中，实现了体内镰刀病的增加。这种小鼠红细胞镰状细胞模型应该有助于提高我们对镰状细胞病的理解，并可能为测试治疗干预提供一个模型。图片
To develop an animal model for sickle cell anemia, we have created transgenic mice that express a severe naturally occurring human sickling hemoglobin, Hb S Antilles. Due to its low solubility and oxygen affinity, Hb S Antilles has a greater propensity to cause red cell sickling than Hb S. To make transgenic animals that express a high level of Hb S Antilles, the erythroid-specific DNAse I hypersensitive site II from the human beta-globin cluster was linked independently to the human alpha 2-globin gene and to the beta S Antilles gene. Embryos were injected with both constructs simultaneously and seven transgenic mice were obtained, three of which contained both the human alpha and the human beta S Antilles transgene. After crossing the human transgenes into the mouse beta-thalassemic background a transgenic mouse line was derived in which approximately half the beta-globin chains in the murine red cells were human beta S Antilles. Deoxygenation of the transgenic red cells in vitro resulted in extensive sickling. An increase of in vivo sickling was achieved by placing these transgenic mice in a low oxygen environment. This murine model for red cell sickling should help to advance our understanding of sickle cell disease and may provide a model to test therapeutic interventions.Images
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单个红细胞特异性 DNase I 超敏感位点可激活转基因小鼠中高水平的人类 β-珠蛋白基因表达。
影响因子：
10.5
作者：
Ryan,TM;Behringer,RR;Martin,NC;Townes,TM;Palmiter,RD;Brinster,RL
通讯作者：
Brinster,RL
转基因小鼠中功能性人血红蛋白的合成。
DOI：
10.1126/science.2772649
发表时间：
1989
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Behringer,RR;Ryan,TM;Reilly,MP;Asakura,T;Palmiter,RD;Brinster,RL;Townes,TM
通讯作者：
Townes,TM
人β-珠蛋白链对β-地中海贫血小鼠红细胞细胞特性的影响。
DOI：
10.1172/jci113670
发表时间：
1988
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Rubin,EM;Kan,YW;Mohandas,N
通讯作者：
Mohandas,N
DOI：
10.1073/pnas.86.18.7082
发表时间：
1989-09
影响因子：
11.1
作者：
Peter T. Curtin;Depei Liu;Wen Liu;JudyC. Chang;Yuet Wai Kan
通讯作者：
Peter T. Curtin;Depei Liu;Wen Liu;JudyC. Chang;Yuet Wai Kan
通过基因转移至种系来纠正小鼠β-地中海贫血。
DOI：
10.1126/science.3461564
发表时间：
1986
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Costantini,F;Chada,K;Magram,J
通讯作者：
Magram,J