| 摘要 |
The present invention relates to telomere-associated chromosome fragmentation by the use of synthetic telomeric DNA constructs comprising a telomeric region, a selectable marker gene and a homologous region, its application in a targeted manner to delete chromosomal regions in eukaryotic cells such as embryonic stem (ES) cells, and the construction of mice in which telomeric regions have been deleted or altered. It is demonstrated that the murine immunoglobulin heavy chain locus located at the telomeric end of chromosome (12) can be entirely deleted by targeted chromosome fragmentation in ES cells using a construct incorporating a human cloned telomeric fragment, and that mice can thereby be produced in which this locus, which is essential for antibody production, is missing.
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