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Chimeric mice derived from human-mouse hybrid cells.

K Illmensee, P C Hoppe, C M Croce

    Proceedings of the National Academy of Sciences of the United States of America
    |April 1, 1978
    PubMed
    Summary
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    Mouse teratocarcinoma cells fused with human cells formed hybrids that differentiated in mice. These human-mouse hybrid cells integrated into developing organs, showing potential for studying human gene expression.

    Area of Science:

    • Developmental Biology
    • Cell Biology
    • Genetics

    Background:

    • Mouse teratocarcinoma cells (OTT6050) were cultured and selected for 5-bromodeoxyuridine (BrdUrd) resistance.
    • These embryonal carcinoma cells differentiated into various tissues in vivo and were deficient for thymidine kinase.

    Purpose of the Study:

    • To create and analyze human-mouse hybrid cells for their differentiation potential in vivo.
    • To investigate the integration and differentiation capacity of hybrid cells following blastocyst injection.

    Main Methods:

    • Fused BrdUrd-resistant mouse teratocarcinoma cells with human fibrosarcoma cells (HT1080-6TG) deficient in hypoxanthine phosphoribosyltransferase.
    • Selected hybrid cells in hypoxanthine/aminopterin/thymidine medium, retaining specific human chromosomes (e.g., chromosome 17).

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  • Injected single hybrid cells into mouse blastocysts and transferred them to foster mothers, analyzing resulting offspring for mosaicism and differentiation.

    • Main Results:

    • Hybrid cells segregated human chromosomes, retaining 1-3, including chromosome 17 carrying thymidine kinase and galactokinase genes.
    • Injected hybrid cells contributed to the development of seven different organs in mosaic mice.
    • Weak human-specific galactokinase activity was detected in some mosaic tissues, but unequivocal human gene product detection was limited.

    Conclusions:

    • Human-mouse hybrid cells retain in vivo differentiation potential after in vitro selection and culture.
    • Blastocyst injection of hybrid cells provides a feasible method to study human gene expression during mammalian development.
    • These findings support the use of hybrid cells for investigating human gene function and differentiation in a developmental context.