Studies of foreign genes transmitted through the germ lines of transgenic mice.

A novel gene transfer system has recently been developed in which DNA sequences isolated by molecular cloning can be introduced and permanently integrated into the genomes of developing mice. The procedure entails the microinjection of such cloned sequences into the pronuclei of one-celled embryos followed by reimplantation into pseudopregnant females for continued development. Although data obtained from this system are still few, they indicate it will have broad applicability to problems of mammalian developmental genetics. In order that such experiments be fully exploited, it will be necessary to understand the behavior of foreign genes introduced into the mouse and the relationship of that behavior to endogenous gene structure, function, and regulation. As a step in this direction, we have examined a line of mice into which has been transferred a recombinant plasmid consisting of a human leukocyte interferon genomic fragment cloned into the BamHI site of pBR322. The donor material has been integrated as a large concatameric structure which is inherited as a single Mendelian trait to several generations of progeny. Crossing of heterozygotes has apparently resulted in the production of viable homozygotes. In one animal, the structure of the integrated fragment was altered in spleen DNA but not in germ cells. This finding may reflect a normal processing mechanism whereby the structure of genes is altered during cell differentiation, or it may mean that transferred DNA does not behave as endogenous genes do.