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Zadelaar, S.M. et al.

Zadelaar, Boesten, Pires, van Nieuwkoop, Biessen, Jukema, Havekes, van Vlijmen, Willems van Dijk,

Local cre-mediated gene recombination in vascular smooth muscle cells in mice.

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-ER(T2)) transgene and a stop-floxed beta-galactosidase gene in the Rosa26 locus: the SM-CreER(T2)(ki)/rosa26 mouse. A dose and time curve of 0-10% (w/w) 4-OHT and 0-14 days application of the PDD in SM-CreER(T2)(ki)/rosa26 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-CreER(T2)(ki)/rosa26 mice without affecting additional SMCs.[1]

References

Local cre-mediated gene recombination in vascular smooth muscle cells in mice. Zadelaar, S.M., Boesten, L.S., Pires, N.M., van Nieuwkoop, A., Biessen, E.A., Jukema, W., Havekes, L.M., van Vlijmen, B.J., Willems van Dijk, K. Transgenic Res. (2006) [Pubmed]

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