Experimental production of transgenic mice carrying human beta-globin genes

To produce transgenic mice carrying human beta-globin genes, we introduced the following two constructs of the genes to male pronuclei of fertilized mouse eggs: 4.4 kb Pst I/Pst I sequences of the human beta-globin gene (experiment 1) and the human beta-globin gene cluster (cosHG 28) containing G gamma, A gamma, delta and beta-globin genes and cosmid vector pJB8 (37.5 kb, experiment 2). In experiment 1, 25 mice were born, and four (one female and three males) carrying the injected gene sequences were identified. One of these mice carried the entire sequence of the human beta-globin gene but three others appeared to carry only a part of the entire sequence. The mouse with the entire sequence showed a slight increase in the minor component of the mouse beta-globin chain in the same position as the human beta-globin chain. In experiment 2, 61 mice were born, and nine (three females and six males) carried the sequences of the injected gene. However, from DNA analysis, no appropriate sequences present within the A gamma- or beta-globin gene were identified in any of the founder mice. In this case, DNA fragments of the gene cluster that were digested in the mouse nucleus after microinjection of the gene might be integrated into host DNA.