Local Cre-Mediated Gene Recombination in Vascular Smooth Muscle Cells in Mice (original) (raw)

Abstract

Here we describe a means to conditionally modify genes at a predefined and localized region of the vasculature using a perivascular drug delivery device (PDD). A 4-hydroxytamoxifen (4-OHT)-eluting PDD was applied around the carotid or femoral artery of a mouse strain carrying both the tamoxifen-inducible and smooth muscle cell (SMC)-specific Cre-recombinase (SM-Cre-ERT2) transgene and a stop-floxed β-galactosidase gene in the Rosa26 locus: the SM-CreERT2(ki)/_rosa_26 mouse. A dose and time curve of 0–10% (w/w) 4-OHT and 0–14 days application of the PDD in SM-CreERT2(ki)/_rosa_26 mice showed optimal gene recombination at 1% (w/w) 4-OHT loading at 7 days post application (carotid artery 2.4±1.8%; femoral artery 4.0±3.8% of SMCs). The unique 4-OHT-eluting PDD allowed us to achieve SMC-specific recombination in the same order of magnitude as compared to systemic tamoxifen administration. In addition, recombination was completely confined to the PDD-treated vessel wall segment. Thus, local application of a 4-OHT-eluting PDD results in vascular SMC-specific Cre-mediated recombination in SM-CreERT2(ki)/_rosa_26 mice without affecting additional SMCs.

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Authors and Affiliations

  1. Department of Cardiology, p/o TNO-Quality of Life Gaubius Laboratory, Leiden University Medical Centre, Zernikedreef 9, P.O. Box 2215, 2301, CE, Leiden, The Netherlands
    Susanne M. Zadelaar, Nuno M. M. Pires & Wouter Jukema
  2. Department of General Internal Medicine, p/o TNO-Quality of Life Gaubius Laboratory, Leiden University Medical Centre, Leiden, The Netherlands
    Lianne S. M. Boesten & Anita van Nieuwkoop
  3. Department of Biopharmacy, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    Erik A. L. Biessen
  4. TNO-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands
    Louis M. Havekes
  5. Hemostasis and Thrombosis Research Center, Leiden University Medical Centre, Leiden, The Netherlands
    Bart J. M. van Vlijmen
  6. Department of Human and Clinical Genetics, Leiden University Medical Centre, Leiden, The Netherlands
    Ko Willems van Dijk

Authors

  1. Susanne M. Zadelaar
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  2. Lianne S. M. Boesten
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  3. Nuno M. M. Pires
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  4. Anita van Nieuwkoop
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  5. Erik A. L. Biessen
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  6. Wouter Jukema
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  7. Louis M. Havekes
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  8. Bart J. M. van Vlijmen
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  9. Ko Willems van Dijk
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Correspondence toSusanne M. Zadelaar.

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These authors contributed equally

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Zadelaar, S.M., Boesten, L.S.M., Pires, N.M.M. et al. Local Cre-Mediated Gene Recombination in Vascular Smooth Muscle Cells in Mice.Transgenic Res 15, 31–36 (2006). https://doi.org/10.1007/s11248-005-3226-z

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