CORRELATION BETWEEN THE DEVELOPMENT OF MURINE MAMMARY CANCER AND THE SEGREGATION OF ENDOGENOUS GENES

Abstract

We have investigated the mouse mammary tumor virus (MMTV) specific proviral DNA content of the C57BL and GR strains of mice by restriction endonuclease digestion of cellular DNA and Southern transfer of DNA fragments to nitrocellulose filter paper. GR mice develop 100% mammary tumors at an early age whereas C57BL mice have less than a one percent incidence. The MMTV containing DNA fragments were identified by hybridization to MMTV [32P] complementary DNA. Digestion of cellular DNA with the restriction endonuclease Pst-1, which generates multiple internal MMTV specific DNA fragments, has identified viral DNA fragments at 2.5 and 0.6 megadaltons in the GR DNA, which are absent in the C57BL DNA. The GR and C57BL mice share Pst-1 restriction fragments at 3.3, 1.1, 0.9 and 0.5 megadaltons. The C57BL mouse has a Pst-1 restriction fragment at 3.1 megadaltons which is absent in DNA from GR mice. Genetic analyses of GR and C57BL crosses has determined that the Pst-1 fragments specific for the GR MMTV are inherited as a single Mendelian unit in [C57BL × (C57BL × GR)F1] backcross mice, i.e., 50 percent of the livers examined contain Pst-1 fragments at 2.5 and 0.6 megadaltons. We have been able to correlate the presence of these MMTV(GR) specific Pst-1 fragments with the occurrence of early mammary tumors in the [C57BL × (C57BL × GR)F1] backcross mice. These studies thus demonstrate the utility of restriction mapping in the diagnosis of a naturally occurring neoplasm.