Germ line integration of Moloney leukemia virus: Identification of the chromosomal integration site

Abstract

The chromosomal integration site of the structural gene of Moloney murine leukemia virus (M-MuLV) in the genome of BALB/Mo mice was mapped genetically. These mice transmit the exogenous M-MuLV as an endogenous virus at a single Mendelian locus. In 1 experiment, non-virus-producing fibroblasts prepared from homozygous BALB/Mo embryos were fused to Chinese hamster Wg3-h-o cells. In an analysis of 30 independent mouse-Chinese hamster cell hybrid clones, the segregation of the viral genome measured by molecular hybridization and enzymes assigned to 16 different mouse chromosomes were compared. A highly concordant segregation of M-MuLV sequences and the mouse enzyme triosephosphate isomerase (TPI, EC 5.3.1.1), whose gene was assigned to chromosome 6, was found. A further karyotype analysis of 9 clones, in which the chromosomes were identified cytochemically, supported this result. In a 2nd experiment, the segregation of the viral genome was studied in backcrosses of BALB/Mo with ABP/J mice. In the backcross ABP/J .times. (ABP/J BALB/Mo) a linkage of the M-MuLV genome to the morphological marker wa-1 on mouse chromosome 6 was found. The M-MuLV genome is apparently integrated in mouse chromosome 6. These experiments define the genetic locus Mov-1, denoting the genetically transmitted structural gene of M-MuLV in BALB/Mo mice.