小鼠主要成年β-珠蛋白基因插入破坏后致死性地中海贫血
Lethal thalassemia after insertional disruption of the mouse major adult beta-globin gene.
作者信息
Shehee W R, Oliver P, Smithies O
机构信息
Department of Pathology, University of North Carolina, Chapel Hill 27599-7525.
出版信息
Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3177-81. doi: 10.1073/pnas.90.8.3177.
Thalassemias are hereditary anemias caused by mutations that disturb the normal 1:1 balance of alpha- and beta-globin chains that form hemoglobin. We have disrupted the major adult beta-globin gene (b1) in mouse embryonic stem cells by using homologous recombination to insert selectable sequences into the gene. Mice homozygous for this insertional disruption of the b1 gene (Hbbth-2/Hbbth-2) are severely anemic and die perinatally. In contrast, approximately 60% of mice homozygous for deletion of the same gene (Hbbth-1/Hbbth-1) survive to adulthood and are much less anemic [Skow, L. C., Burkhart, B. A., Johnson, F. M., Popp, R. A., Goldberg, S. Z., Anderson, W. F., Barnett, L. B. & Lewis, S. E. (1983) Cell 34, 1043-1052]. These different phenotypes have implications for the control of beta-globin gene expression.
地中海贫血是由突变引起的遗传性贫血，这些突变会扰乱形成血红蛋白的α-和β-珠蛋白链的正常1:1平衡。我们通过同源重组将选择序列插入小鼠胚胎干细胞中的主要成人β-珠蛋白基因（b1），从而破坏了该基因。该b1基因插入性破坏的纯合小鼠（Hbbth-2/Hbbth-2）严重贫血，并在围产期死亡。相比之下，同一基因缺失的纯合小鼠（Hbbth-1/Hbbth-1）约60%存活至成年，贫血程度也轻得多[Skow, L. C., Burkhart, B. A., Johnson, F. M., Popp, R. A., Goldberg, S. Z., Anderson, W. F., Barnett, L. B. & Lewis, S. E. (1983) Cell 34, 1043 - 1052]。这些不同的表型对β-珠蛋白基因表达的调控具有重要意义。
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