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Lethal α–thalassaemia created by gene targeting in mice and its genetic rescue

Abstract

Mutations at the α–globin locus are the most common class of mutations in humans, with deletion of all four adult α–globin genes resulting in the perinatal lethal condition haemoglobin Bart's hydrops fetalis. Using gene targeting in mice, we have deleted a 16 kilobase region encompassing both adult α–globin genes. Animals homozygous for this deletion become hydropic and die late in gestation mimicking humans with hydrops fetalis. Introduction of a human α–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.

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Pászty, C., Mohandas, N., Stevens, M. et al. Lethal α–thalassaemia created by gene targeting in mice and its genetic rescue. Nat Genet 11, 33–39 (1995). https://doi.org/10.1038/ng0995-33

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