Inactivation of mouse α-globin gene by homologous recombination: Mouse model of hemoglobin H disease

Abstract

We have disrupted the 5' locus of the duplicated adult α-globin genes by gene targeting in the mouse embryonic stem cells and created mice with α- thalassemia syndromes. The heterozygous knockout mice (-α/αα) are asymptomatic like the silent carriers in humans whereas the homozygous knockout mice (-α/-α) show hemolytic anemia. Mice with three dysfunctional α-globin genes generated by breeding the 5' α-globin knockouts (-α/αα) and the deletion type α-thalassemia mice (--/αα) produce severe hemoglobin H disease and they die in utero. These results indicate that the 5' α- globin gene is the predominant locus in mice, and suggest that it is even more dominant than its human homologue.