A MOUSE MODEL FOR BETA-THALASSEMIA
A MOUSE MODEL FOR BETA-THALASSEMIA
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DOI：
10.1016/0092-8674(83)90562-7
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发表时间：
1983-01-01
期刊：
影响因子：
64.5
通讯作者：
LEWIS, SE
中科院分区：
文献类型：
--
作者：
SKOW, LC;BURKHART, BA;LEWIS, SE
产生正常β绝对缺乏的突变-从DBA/2 J雄性小鼠中回收主要珠蛋白多肽。大多数缺乏症的纯合子小鼠存活至成年并繁殖，但出生时比同窝出生的小鼠小，表现出低色素性小细胞性贫血伴严重红细胞大小不等、红细胞异形和网织红细胞增多症，并且在高比例的循环红细胞中存在包涵体。该缺陷的杂合子小鼠表现出轻度网织红细胞增多症，但临床上没有贫血。通过3 H-Leu掺入的体外珠蛋白链合成分析揭示了β-在杂合子中珠蛋白合成接近正常（95%），在缺乏纯合子中约为正常的75%。通过限制性酶切分析对突变的分子表征揭示了约3.3kb的DNA缺失，包括调节序列和β-半乳糖苷酶的所有编码区。主要珠蛋白。基于遗传和血液学标准，命名为Hbbth-1的突变等位基因纯合小鼠代表β-Hbbth-1的第一个动物模型。地中海贫血（库利氏贫血），一种严重的人类遗传性疾病。
A mutation that produces an absolute deficiency of normal .beta.-major globin polypeptides was recovered from a DBA/2J male mouse. Most mice homozygous for the deficiency survived to adulthood and reproduced but were smaller at birth than their littermates and demonstrated a hypochromic microcytic anemia with severe anisocytosis, poikilocytosis and reticulocytosis and the presence of inclusion bodies in a high proportion of circulating erythrocytes. Mice heterozygous for the deficiency demonstrated a mild reticulocytosis but were not clinically anemic. Analysis of globin chain synthesis in vitro by 3H-Leu incorporation revealed that .beta.-globin synthesis was nearly normal (95%) in heterozygotes and about 75% of normal in deficiency homozygotes. Molecular characterization of the mutation by restriction analysis revealed a deletion of about 3.3 kb [kilobase] of DNA, including regulatory sequences and all coding blocks for .beta.-major globin. Based on genetic and hematological criteria, mice homozygous for the mutant allele, designated Hbbth-1, represent the 1st animal model of .beta.-thalassemia (Cooley''s anemia), a severe genetic disease of humans.