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Comparison of endothelial promoter efficiency and specificity in mice reveals a subset of Pdgfb-positive hematopoietic cells.

dc.rights.licenseopenen_US
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorKILANI, Badr
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGOURDOU-LATYSZENOK, Virginie
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGUY, Alexandre
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorBATS, Marie-Lise
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorPEGHAIRE, Claire
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorPARRENS, Marie
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorRENAULT, Marie-Ange
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorDUPLÀA, Cecile
dc.contributor.authorVILLEVAL, Jean-Luc
dc.contributor.authorRAUTOU, Pierre-Emmanuel
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCOUFFINHAL, Thierry
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorJAMES, Chloe
dc.date.accessioned2021-04-12T08:56:04Z
dc.date.available2021-04-12T08:56:04Z
dc.date.issued2019-01-01
dc.identifier.issn1538-7836en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/26920
dc.description.abstractEnEssentials To reliably study the respective roles of blood and endothelial cells in hemostasis, mouse models with a strong and specific endothelial expression of the Cre recombinase are needed. Using mT/mG reporter mice and conditional JAK2 mice, we compared Pdgfb-iCreERT2 and Cdh5(PAC)-CreERT2 with well-characterized Tie2-Cre mice. Comparison of recombination efficiency and specificity towards blood lineage reveals major differences between endothelial transgenic mice. Cre-mediated recombination occurs in a small number of adult hematopoietic stem cells in Pdgfb-iCreERT2;JAK2 transgenic mice. SUMMARY: Background The vessel wall, and particularly blood endothelial cells (BECs), are intensively studied to better understand hemostasis and target thrombosis. To understand the specific role of BECs, it is important to have mouse models that allow specific and homogeneous expression of genes of interest in all BEC beds without concomitant expression in blood cells. Inducible Pdgfb-iCreERT2 and Cdh5(PAC)-CreERT2 transgenic mice are widely used for BEC targeting. However, issues remain in terms of recombination efficiency and specificity regarding hematopoietic cells. Objectives To determine which mouse model to choose when strong expression of a transgene is required in adult BECs from various organs, without concomitant expression in hematopoietic cells. Methods Using mT/mG reporter mice to measure recombination efficiency and conditional JAK2 mice to assess specificity regarding hematopoietic cells, we compared Pdgfb-iCreERT2 and Cdh5(PAC)-CreERT2 with well-characterized Tie2-Cre mice. Results Adult Cdh5(PAC)-CreERT2 mice are endothelial specific but require a dose of 10 mg of tamoxifen to allow constant Cre expression. Pdgfb-iCreERT2 mice injected with 5 mg of tamoxifen are appropriate for most endothelial research fields except liver studies, as hepatic sinusoid ECs are not recombined. Surprisingly, 2 months after induction of Cre-mediated recombination, all Pdgfb-iCreERT2;JAK2 mice developed a myeloproliferative neoplasm that is related to the presence of JAK2V617F in hematopoietic cells, showing for the first time that Cre-mediated recombination occurs in a small number of adult hematopoietic stem cells in Pdgfb-iCreERT2 transgenic mice. Conclusion This study provides useful guidelines for choosing the best mouse line to study the role of BECs in hemostasis and thrombosis.
dc.language.isoENen_US
dc.subject.enAlleles
dc.subject.enAnimals
dc.subject.enBrain
dc.subject.enEndothelial Cells
dc.subject.enHematopoietic Stem Cells
dc.subject.enHemostasis
dc.subject.enIntegrases
dc.subject.enKidney
dc.subject.enLiver
dc.subject.enLung
dc.subject.enLymphokines
dc.subject.enMice
dc.subject.enMice
dc.subject.enTransgenic
dc.subject.enMyocardium
dc.subject.enPlatelet-Derived Growth Factor
dc.subject.enPolymerase Chain Reaction
dc.subject.enRetina
dc.subject.enTamoxifen
dc.subject.enThrombosis
dc.title.enComparison of endothelial promoter efficiency and specificity in mice reveals a subset of Pdgfb-positive hematopoietic cells.
dc.title.alternativeJ Thromb Haemosten_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1111/jth.14417en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologie/Cardiologie et système cardiovasculaireen_US
dc.identifier.pubmed30801958en_US
bordeaux.journalJournal of Thrombosis and Haemostasisen_US
bordeaux.page827-840en_US
bordeaux.volume17en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-03195843
hal.version1
hal.date.transferred2021-04-12T08:56:11Z
hal.exporttrue
workflow.import.sourcepubmed
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