LETHAL ALPHA-THALASSEMIA CREATED BY GENE TARGETING IN MICE AND ITS GENETIC RESCUE

Mutations at the alpha-globin locus are the most common class of mutat ions in humans, with deletion of all four adult alpha-globin genes res ulting in the perinatal lethal condition haemoglobin Bart's hydrops fe talis. Using gene targeting in mice, we have deleted a 16 kilobase reg ion encompassing both adult alpha-globin genes. Animals homozygous for this deletion become hydropic and die late in gestation mimicking hum ans with hydrops fetalis. Introduction of a human alpha-globin transge ne rescued these animals from perinatal death thus demonstrating the u tility of this murine model in the development of cellular and gene ba sed approaches for treating this human genetic disease.