A 191-kb genomic fragment containing the human α-globin locus can rescue α-thalassemic mice

Abstract

A 191-kb human bacterial artificial chromosome (BAC) containing the human α-globin genomic locus was used to generate transgenic mice that express, exclusively, human α-globin (huα-globin). Expression of huα-globin reaches a level of 36% of that of endogenous mouse α-globin (muα-globin) on a heterozygous mouse α-thalassemia background (muα-globin knockout, muα+/-). Hemizygous transgenic mice carrying the huα-globin locus on a heterozygous knockout background ( huα+/0, muα++/ -) demonstrated complementation of most hematologic parameters. By crossing huα+/0, muα++/ - mice, we were able to generate mice entirely dependent on huα-globin synthesis. Breeding and fluorescent in situ hybridization ..