Renin-promoter SV40 large T-antigen transgenes induce tumors irrespective of normal cellular expression of renin genes.

Chimeric genes containing the 5'-flanking regions of the mouse renin genes, Ren1 and Ren2, associated with the early region of the simian virus 40 (SV40) were constructed. The two recombinant genes which contain, respectively, 0.45- and 2.5-kb the Ren1 and Ren2 5'-flanking sequences, named Ren1Tag and Ren2Tag, were microinjected into fertilized eggs. Tumors arose after a latency of 5-9 months in mouse lines harboring these hybrid genes except for one, in which a different and earlier pathology was observed (peripheral neuropathies). Most of the pathologies developed by these transgenic mice reflect the tumorigenic spectrum of the SV40 early region gene (choroid plexus, kidney, intestinal tumors, and peripheral neuropathies). None of these tumors arose from renin-producing cells nor produced renin. As suggested by the tumor pathology, the expression of the SV40 large T-antigen did not follow the normal expression of the Ren1 and the Ren2 genes since SV40 large T-antigen mRNA was found in tissues which normally do not express renin.