MOLONEY LEUKEMIA-VIRUS GENE-EXPRESSION AND GENE AMPLIFICATION IN PRELEUKEMIC AND LEUKEMIC BALB-MO MICE

Mice carrying the exogenous Moloney leukemia virus (M-MuLV) as an endogenous virus have been derived previously. This mouse strain (BALB/Mo) transmits the virus as a single Mendelian gene (Mov-1 locus) from one generation to the next. Molecular hybridization experiments were performed to identify the organs in which the M-MuLV gene is activated during postnatal life of BALB/Mo mice and to determine the age-dependent onset of M-MuLV gene expression. Spleen and thymus cells of BALB/Mo mice synthesize M-MuLV-specific RNA soon after birth and virus gene expression reaches high levels at 3-4 weeks of age. A substantial further increase in virus gene expression is not observed in leukemic tissues of older animals. Other organs, such as liver, brain, and kidneys, do not express M-MuLV-specific RNA throughout the animals' life. These observations define lymphatic tissues (spleen and thymus) as the target organs of M-MuLV expression in BALB/Mo mice. Virus gene expression was correlated with somatic amplification of M-MuLV-specific DNA sequences during the preleukemic and leukemic phase of the animals' life. DNA amplification occurs in two steps in target tissues of BALB/Mo mice. A first step to approximately two copies per haploid genome equivalent is observed in preleukemic mice and a second step to three to four copies is observed in leukemic tissues. Nontarget tissues carry one copy of M-MuLV-specific DNA sequences regardless of the age of the animal. These results suggest that M-MuLV-specific gene expression is not sufficient for leukemic transformation and is related to virus-specific DNA amplification in preleukemic animals. A second amplification of M-MuLV DNA sequences appears to be related to leukemic transformation. © 1979.