ArticleTransgenic research2009
A caveat in mouse genetic engineering: ectopic gene targeting in ES cells by bidirectional extension of the homology arms of a gene replacement vector carrying human PARP-1.
Article in Transgenic research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
4 citing papers in PubMed, 14 citations in OpenAlex.
- The precision strategy of human genome correction via a set of circular donor DNA and its cleaver.Frontiers in genome editing · 2026Article
- Article
- CRISPR/Cas-mediated genome editing in the rat via direct injection of one-cell embryos.Nature protocols · 2014Article
- Efficient gene targeting mediated by a lentiviral vector-associated meganuclease.Nucleic acids research · 2011Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Here we report an approach to generate a knock-in mouse model using an 'ends-out' gene replacement vector to substitute the murine Parp-1 (mParp-1) coding sequence (32 kb) with its human orthologous sequence (46 kb). Unexpectedly, examination of mutant ES cell clones and mice revealed that site-specific homologous recombination was mimicked in three independently generated ES cell clones by bidirectional extension of the vector homology arms using the endogenous mParp-1-flanking sequences as templates. This was followed by adjacent integration of the targeting vector, thus leaving the endogenous mParp-1 locus functional. A related phenomenon termed 'ectopic gene targeting' has so far only been described for 'ends-in' integration-type vectors in non-ES cell gene targeting. We provide reliable techniques to detect such ectopic gene targeting which represents an unexpected caveat in mouse genetic engineering that should be considered in the design and validation strategy of future gene knock-in approaches.
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