Infection of preimplantation mouse embryos and of newborn mice with leukemia virus: tissue distribution of viral DNA and RNA and leukemogenesis in the adult animal

Abstract

Explanted mouse embryos derived from low leukemia incidence strains were infected with Moloney murine leukemia virus (M-MuLV) at the 4-8 cell stage of development. After cultivation in vitro to the blastocyst stage, the embryos were surgically transferred to the uteri of pseudo-pregnant surrogate mothers. Of 15 animals born, one developed a leukemia at 8 weeks of age. When autopsied, this leukemia was found to be of the lymphatic type, as is typical for the M-MuLV-induced disease. In addition, infectious M-MuLV virus was isolated from the serum. Molecular hybridization tests for the presence of M-MuLV-specific sequences were conducted on DNA and RNA extracted from eight different organs. The DNA-DNA reannealing experiments revealed the presence of two classes of M-MuLV-specific sequences in equal concentrations in all tissues tested. The less abundant class of M-MuLV-specific sequences was not detected in tissues from uninfected animals or in non-target tissues of leukemic animals infected at birth. The results are consistent with the working hypothesis that the virus was integrated in all cells of the animal, possibly including the germ line. Fifty to 100 times more M-MuLV-specific RNA was detected in tumor tissues than was found in non-target organs such as liver, brain, and testes. Since all organs contained the same amount of virus-specific DNA, these results indicate that the M-MuLV-specific DNA can be differentially expressed in different tissues.