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Long-range chromosomal engineering is more efficient in vitro than in vivo
Lisa E Olson1, Jason Tien, Sarah South
1Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Transgenic Research
|September 9, 2005
Summary
Targeted meiotic recombination (TAMERE) is ineffective for large chromosomal rearrangements in mice. An in vitro method successfully created a translocation, yielding mouse models for Down syndrome research.
Area of Science:
- Genetics
- Genomics
- Developmental Biology
Background:
- Cre/LoxP systems are crucial for chromosomal engineering in embryonic stem (ES) cells, enabling the creation of aneuploidy models.
- Targeted meiotic recombination (TAMERE) was developed as an in vivo method for Cre-mediated recombination during male meiosis in transgenic mice.
Purpose of the Study:
- To evaluate the efficacy of TAMERE for large-scale chromosomal engineering (3.9 Mb) in mouse Chromosome 16 (MMU16).
- To develop an effective method for generating chromosomal translocations for Down syndrome research.
Main Methods:
- Testing TAMERE for in vivo deletion and translocation induction with LoxP sites 3.9 Mb apart on MMU16.
- Utilizing an in vitro method to achieve the desired reciprocal duplication/deletion of MMU16.
Main Results:
- TAMERE was ineffective in generating chromosomal deletions or translocations in vivo for large genomic distances.
- An in vitro approach successfully created the targeted translocation in ES cells.
- Mice with MMU16 alterations homologous to human chromosome 21 were generated.
Conclusions:
- TAMERE has limited utility for large genomic rearrangements.
- In vitro methods are effective for chromosomal engineering in ES cells.
- The generated mouse models are valuable for studying Down syndrome.