Trisomy eight in ES cells is a common potential problem in gene targeting and interferes with germ line transmission

Xin Liu, Hong Wu, Janet Loring, Sheriar Hormuzdi, Christine M. Disteche, Paul Bornstein, Rudolph Jaenisch

    Research output: Contribution to journalArticlepeer-review

    142 Citations (Scopus)

    Abstract

    The ability to contribute to the germ line is the most important experimental feature of embryonic stem (ES) cells. Using ES cells, it is possible to introduce targeted mutations into any gene and to derive the corresponding mutant mice. A common problem with this technology is that the ES cells often lack or have only a low efficiency of germ line transmission. To address this issue, we examined the relationship between the growth rate and karyotype of ES cells, and their ability to contribute to the germ line. We found that chromosomal abnormalities occurred rather frequently in ES cells. Cells having an abnormal number of chromosomes, in particular trisomy 8, were found in three independently derived ES cell lines, and this abnormality conferred a selective growth advantage on these cells. Selection of abnormal cells led to depletion and eventual loss of normal ES cells during consecutive passages. In comparison with parental ES cells, ES cells with trisomy 8 contributed rarely to the germ line. This realization allowed us to select, based upon ES cell clone morphology, those clones with the highest probability of contributing to the germ line. This insight is of practical value for any given gene targeting experiment as it permits optimization of the rate of success without having to rely on more elaborate tests such as karyotyping individual clones prior to blastocyst injection.
    Original languageEnglish
    Pages (from-to)85-91
    Number of pages7
    JournalDevelopmental Dynamics
    Volume209
    Issue number1
    DOIs
    Publication statusPublished - 1 May 1997

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