The Expression of Human α-like Globin Genes in Transgenic Mice Mediated by Bacterial Artificial Chromosome

After screening a bacterial artificial chromosome of human genomic DNA library with human HS-40, ζ-, α-, and γ-globin probes, a 110-kb clone bearing the whole human α-globin gene cluster was obtained and rare restriction endonuclease mapping was performed. The bacterial artificial chromosome DNA was isolated, and transgenic mice were generated. Three founders were detected from 35 newborn mice. The copy numbers were 1, 2, and 2, and the expression of human α-globin genes in various tissues at different developmental stages in the transgenic mice was assayed. The human α-globin mRNA can be detected in bone marrow, kidney, liver, brain, but not in muscle, testis, or thymus. The human ζ-globin genes were switched off, and the α-globin genes were switched at day 11.5 in mouse embryo, indicating that developmental stage-specific expression of the α-like globin genes was properly regulated. The human α-globin mRNA ranged between 17-68% of the endogenous mouse α-globin, suggesting that the expression of human α-globin genes is integration site-dependent in transgenic mice. The ratio of human α2- and α1- globin gene expression in adult transgenic mouse is about 2.5:1 similar to the expression in human.