Long-range chromosomal engineering is more efficient in vitro than in vitro

Lisa E. Olson, Jason Tien, Sarah South, Roger H. Reeves

Research output: Contribution to journalArticlepeer-review

Abstract

Cre/LoxP mediated chromosomal engineering in embryonic stem (ES) cells has a variety of applications, including the creation of model systems for studying aneuploidy. Targeted meiotic recombination (TAMERE) was proposed as a high efficiency in vivo alternative to effect Cre-mediated recombination, in which Cre recombinase under control of the Synaptonemal Complex 1 promoter is expressed during male meiosis in transgenic mice. TAMERE has been successfully used with LoxP sites up to 100 kb apart. We tested TAMERE for a chromosome engineering application in which LoxP sequences were integrated into sites 3.9 Mb apart on the same (cis) or opposite (trans) copies of mouse Chromosome 16 (MMU16). TAMERE was ineffective in generating either a deletion or a translocation in vivo. The TAMERE method may be of limited use for large genomic rearrangements. The desired translocation was achieved with an in vitro method that can be used in any ES cell line. Mice produced from the reciprocal duplication/deletion of MMU16 in a region homologous to human chromosome 21 provide models that are useful in studies of Down syndrome.

Original languageEnglish (US)
Pages (from-to)325-332
Number of pages8
JournalTransgenic Research
Volume14
Issue number3
DOIs
StatePublished - Jun 2005

Keywords

  • Chromosome engineering
  • Cre/LoxP
  • Down syndrome
  • TAMERE
  • Targeted meiotic recombination

ASJC Scopus subject areas

  • Biotechnology
  • Animal Science and Zoology
  • Agronomy and Crop Science
  • Genetics

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