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Recombinant Retroviral Production and Infection of B Cells
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Chromosomal position and activation of retroviral genomes inserted into the germ line of mice

R Jaenisch, D Jähner, P Nobis

    Cell
    |May 1, 1981
    PubMed

    Insights

    Researchers inserted Moloney leukemia virus (M-MuLV) into mouse germ lines, creating new substrains. The chromosomal integration site significantly influences M-MuLV expression patterns during development.

    Area of Science:

    • Virology
    • Genetics
    • Developmental Biology

    Background:

    • Exogenous Moloney leukemia virus (M-MuLV) was introduced into the mouse germ line via embryo exposure.
    • This generated mosaic mice with integrated M-MuLV at various developmental stages.
    • Previous work established substrains Mov-1 to Mov-4.

    Purpose of the Study:

    • To derive and characterize new mouse substrains harboring M-MuLV in their germ line.
    • To investigate the influence of M-MuLV integration site on viral gene expression.
    • To compare different viral activation and expression phenotypes.

    Main Methods:

    • Exposing mouse embryos to M-MuLV at different embryogenesis stages.
    • Deriving new substrains (Mov-5 to Mov-13) with single integrated M-MuLV genomes.
    • Utilizing restriction enzyme analysis to assess proviral genome integrity.
    • Comparing viral activation timing and expression patterns between substrains.

    Main Results:

    • Nine new substrains (Mov-5 to Mov-13) were established, each with M-MuLV integrated at a unique chromosomal location.
    • Most integrated proviruses showed no major rearrangements, except in Mov-4 and Mov-6.
    • Distinct viral activation phenotypes were observed: early embryogenesis (Mov-13), post-natal (Mov-1), late in life, or no expression.
    • Mov-13 activated virus during embryogenesis, affecting all adult tissues, while Mov-1 activated post-birth, primarily in lymphatic organs.

    Conclusions:

    • The chromosomal location of M-MuLV integration is a critical determinant of its expression during mouse development and differentiation.
    • At least four distinct M-MuLV expression phenotypes can be identified across the 13 substrains.
    • This study provides a valuable resource for understanding retroviral integration and host gene regulation.

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