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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. Two independent experimental approaches were used: (i) 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. We found a highly concordant segregation of M-MuLV sequences and the mouse enzyme triosephosphate isomerase (TPI, EC 5.3.1.1), whose gene has been assigned to chromosome 6. A further karyotype analysis of 9 clones, in which the chromosomes were identified cytochemically, supported this result. (ii) The segregation of the viral genome was studied in backcrosses of BALB/Mo with ABP/J mice. In the backcross ABP/Jx(ABP/JxBALB/Mo) a linkage of the M-MuLV genome to the morphological marker wa-1 on mouse chromosome 6 was found. This confirmed the conclusion that the M-MuLV genome is 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.
Insights
Researchers mapped the Moloney murine leukemia virus (M-MuLV) gene in BALB/Mo mice. The M-MuLV genome integrates into mouse chromosome 6, defining the genetic locus Mov-1 for this endogenous virus.
Area of Science:
- Genetics
- Virology
- Molecular Biology
Background:
- BALB/Mo mice carry the Moloney murine leukemia virus (M-MuLV) as an endogenous virus.
- Understanding the integration site of M-MuLV is crucial for studying retroviral genetics and transmission.
Purpose of the Study:
- To genetically map the chromosomal integration site of the M-MuLV structural gene in BALB/Mo mice.
- To identify the specific mouse chromosome and locus associated with endogenous M-MuLV transmission.
Main Methods:
- Somatic cell hybridization: Fusing M-MuLV-producing mouse fibroblasts with Chinese hamster cells, followed by analysis of viral genome segregation using molecular hybridization.
- Linkage analysis: Studying the segregation of the M-MuLV genome in backcrosses of BALB/Mo mice with ABP/J mice, using morphological markers.
Main Results:
- Concordant segregation of M-MuLV sequences with the mouse enzyme triosephosphate isomerase (TPI) gene, assigned to chromosome 6.
- Linkage of the M-MuLV genome to the wa-1 marker on mouse chromosome 6 in backcross experiments.
- Identification of the genetic locus Mov-1 for the integrated M-MuLV structural gene.
Conclusions:
- The structural gene of M-MuLV is integrated into mouse chromosome 6.
- The genetic locus Mov-1 represents the site of endogenous M-MuLV integration in BALB/Mo mice.
- This mapping provides a foundation for further research into M-MuLV genetics and pathogenesis.