Pászty C, Mohandas N, Stevens M E, Loring J F, Liebhaber S A, Brion C M, Rubin E M
Human Genome Center, Lawrence Berkeley Laboratory, University of California, Berkeley 94720, USA.
Nat Genet. 1995 Sep;11(1):33-9. doi: 10.1038/ng0995-33.
Mutations at the alpha-globin locus are the most common class of mutations in humans, with deletion of all four adult alpha-globin genes resulting in the perinatal lethal condition haemoglobin Barts hydrops fetalis. Using gene targeting in mice, we have deleted a 16 kilobase region encompassing both adult alpha-globin genes. Animals homozygous for this deletion become hydropic and die late in gestation mimicking humans with hydrops fetalis. Introduction of a human alpha-globin transgene rescued these animals from perinatal death thus demonstrating the utility of this murine model in the development of cellular and gene based approaches for treating this human genetic disease.
α-珠蛋白基因座的突变是人类最常见的突变类型，所有四个成人α-珠蛋白基因的缺失会导致围产期致死性疾病——血红蛋白巴氏水肿胎儿综合征。通过对小鼠进行基因靶向操作，我们删除了一个包含两个成人α-珠蛋白基因的16千碱基区域。该缺失纯合子动物会出现水肿，并在妊娠后期死亡，类似于患有水肿胎儿综合征的人类。引入人类α-珠蛋白转基因可使这些动物免于围产期死亡，从而证明了该小鼠模型在开发治疗这种人类遗传病的细胞和基因疗法中的实用性。
