Introduction of a rabbit β-globin gene into the mouse germ line

Abstract

The introduction of cloned foreign genes into cultured mammalian cells^1–7 has been used to identify DNA sequences required for correct transcription in vivo^8–10. It is not clear, however, to what extent these systems will be useful for an analysis of the sequences necessary for tissue-specific gene expression. A more appropriate approach for such an analysis might be the production of mice that contain a cloned foreign gene in all their cells, throughout development. This could be accomplished by the transfer of a cloned gene into germ-line cells, and the subsequent transmission of that gene to offspring. Previously, SV40 DNA sequences¹¹ and a cloned HSV-1 thymidine kinase gene¹² have been introduced into somatic tissues of mice by microinjection of the DNAs into blastocysts¹¹ or eggs¹², but germ-line transmission of these sequences has not been demonstrated. The only foreign DNA sequences which have been transferred into and transmitted by the mouse germ-line have been exogenous Moloney leukaemia virus genomes introduced by viral infection of early embryos¹³. We now report the introduction of a cloned rabbit DNA fragment containing the adult β-globin gene into the germ-line of mice. We have analysed 24 mice derived from eggs microinjected with this DNA. Nine mice contain the rabbit β-globin gene in liver DNA, and at least four males from this group transmit the gene to a fraction of their progeny.