@article{Mangerich2009cavea-8047,
  year={2009},
  doi={10.1007/s11248-008-9228-x},
  title={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},
  number={2},
  volume={18},
  issn={0962-8819},
  journal={Transgenic Research},
  pages={261--279},
  author={Mangerich, Aswin and Scherthan, Harry and Diefenbach, Jörg and Kloz, Ulrich and Hoeven, Franciscus van der and Beneke, Sascha and Bürkle, Alexander}
}

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    <dc:creator>Scherthan, Harry</dc:creator>
    <dc:contributor>Diefenbach, Jörg</dc:contributor>
    <dc:contributor>Hoeven, Franciscus van der</dc:contributor>
    <dc:language>eng</dc:language>
    <dcterms:abstract xml:lang="eng">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.</dcterms:abstract>
    <dc:contributor>Kloz, Ulrich</dc:contributor>
    <dc:creator>Kloz, Ulrich</dc:creator>
    <dc:contributor>Beneke, Sascha</dc:contributor>
    <dc:creator>Diefenbach, Jörg</dc:creator>
    <dc:rights>Attribution-NonCommercial-NoDerivs 2.0 Generic</dc:rights>
    <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:39:31Z</dc:date>
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    <dc:creator>Mangerich, Aswin</dc:creator>
    <dc:contributor>Mangerich, Aswin</dc:contributor>
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    <dc:creator>Bürkle, Alexander</dc:creator>
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    <dcterms:issued>2009</dcterms:issued>
    <dcterms:title>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</dcterms:title>
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    <dcterms:bibliographicCitation>First publ. in: Transgenic Research 18 (2009), 2, pp. 261-279</dcterms:bibliographicCitation>
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    <dc:contributor>Bürkle, Alexander</dc:contributor>
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    <dc:creator>Beneke, Sascha</dc:creator>
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    <dc:contributor>Scherthan, Harry</dc:contributor>
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    <dc:creator>Hoeven, Franciscus van der</dc:creator>
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