Local cre-mediated gene recombination in vascular smooth muscle cells in mice
article
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)/rosa26 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)/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. © Springer 2006. Chemicals / CAS: 4 hydroxytamoxifen, 65213-48-1, 68392-35-8; tamoxifen, 10540-29-1; 4-hydroxytamoxifen, 68392-35-8; Cre recombinase, 2.7.7.-; Integrases, 2.7.7.-; Tamoxifen, 10540-29-1
Topics
Biomedical Research4-hydroxytamoxifenCre/loxPLocalPolymer delivery deviceRosa26Smooth muscle4 hydroxytamoxifen4-hydroxytamoxifenCre recombinaseDrug derivativeTamoxifenAnimalCytologyDrug delivery systemDrug effectGenetic recombinationGeneticsGetabolismMousePathologyPhysiologyPromoter regionSmooth muscle fiberTransgenic mousevascular smooth muscleAnimalsDrug Delivery SystemsIntegrasesMiceMice, TransgenicMuscle, Smooth, VascularMyocytes, Smooth MusclePromoter Regions, GeneticRecombination, GeneticTamoxifen
TNO Identifier
239124
ISSN
09628819
Source
Transgenic Research, 15(1), pp. 31-36.
Pages
31-36
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