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http://purl.uniprot.org/citations/29764841http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/29764841http://www.w3.org/2000/01/rdf-schema#comment"

Rationale

Organs of the body require vascular networks to supply oxygen and nutrients and maintain physiological function. The blood vessels of different organs are structurally and functionally heterogeneous in nature. To more precisely dissect their distinct in vivo function in individual organs, without potential interference from off-site targets, it is necessary to genetically target them in an organ-specific manner.

Objective

The objective of this study was to generate a genetic system that targets vascular endothelial cells in an organ- or tissue-specific manner and to exemplify the potential application of intersectional genetics for precise, target-specific gene manipulation in vivo.

Methods and results

We took advantage of 2 orthogonal recombination systems, Dre-rox and Cre-loxP, to create a genetic targeting system based on intersectional genetics. Using this approach, Cre activity was only detectable in cells that had expressed both Dre and Cre. Applying this new system, we generated a coronary endothelial cell-specific Cre (CoEC-Cre) and a brain endothelial cell-specific Cre (BEC-Cre). Through lineage tracing, gene knockout and overexpression experiments, we demonstrated that CoEC-Cre and BEC-Cre efficiently and specifically target blood vessels in the heart and brain, respectively. By deletion of vascular endothelial growth factor receptor 2 using BEC-Cre, we showed that vascular endothelial growth factor signaling regulates angiogenesis in the central nervous system and also controls the integrity of the blood-brain barrier.

Conclusions

We provide 2 examples to illustrate the use of intersectional genetics for more precise gene targeting in vivo, namely manipulation of genes in blood vessels of the heart and brain. More broadly, this system provides a valuable strategy for tissue-specific gene manipulation that can be widely applied to other fields of biomedical research."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.org/dc/terms/identifier"doi:10.1161/circresaha.118.312981"xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Huang X."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Liu Q."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Han X."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Li Y."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Tian X."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Yang X."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Yu Z."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Zhang H."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Zhang L."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Zhou B."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"He L."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Pu W."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Smart N."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/author"Wang Q.D."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/date"2018"xsd:gYear
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/name"Circ Res"xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/pages"86-99"xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/title"Genetic Targeting of Organ-Specific Blood Vessels."xsd:string
http://purl.uniprot.org/citations/29764841http://purl.uniprot.org/core/volume"123"xsd:string
http://purl.uniprot.org/citations/29764841http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/29764841
http://purl.uniprot.org/citations/29764841http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/29764841
http://purl.uniprot.org/uniprot/#_D3Z7S6-mappedCitation-29764841http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/29764841
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