Comparison of endothelial promoter efficiency and specificity in mice reveals a subset of Pdgfb‐positive hematopoietic cells
Author(s): ,
Badr Kilani
Affiliations:
Biology of Cardiovascular Diseases, University of Bordeaux, UMR 1034, INSERM, Pessac, France
,
Virginie Gourdou‐Latyszenok
Affiliations:
Biology of Cardiovascular Diseases, University of Bordeaux, UMR 1034, INSERM, Pessac, France
,
Alexandre Guy
Affiliations:
Biology of Cardiovascular Diseases, University of Bordeaux, UMR 1034, INSERM, Pessac, France
,
Marie‐Lise Bats
Affiliations:
Biology of Cardiovascular Diseases, University of Bordeaux, UMR 1034, INSERM, Pessac, France
,
Claire Peghaire
Affiliations:
Biology of Cardiovascular Diseases, University of Bordeaux, UMR 1034, INSERM, Pessac, France
,
Marie Parrens
Affiliations:
Laboratoire d'Anatomopathologie, CHU de Bordeaux, Pessac, France
,
Marie‐Ange Renault
Affiliations:
Biology of Cardiovascular Diseases, University of Bordeaux, UMR 1034, INSERM, Pessac, France
,
Cecile Duplàa
Affiliations:
Biology of Cardiovascular Diseases, University of Bordeaux, UMR 1034, INSERM, Pessac, France
,
Jean‐Luc Villeval
Affiliations:
University Paris XI, INSERM U1170, Villejuif, France
,
Pierre‐Emmanuel Rautou
Affiliations:
Service d'Hépatologie, Hôpital Beaujon, Assistance Publique‐Hôpitaux de Paris, Clichy, France
,
Thierry Couffinhal
Affiliations:
Biology of Cardiovascular Diseases, University of Bordeaux, UMR 1034, INSERM, Pessac, France. service des Maladies Cardiaques et Vasculaires, CHU de Bordeaux, Pessac, France
Chloe James
Affiliations:
Biology of Cardiovascular Diseases, University of Bordeaux, UMR 1034, INSERM, Pessac, France. Laboratoire d'Hématologie, CHU de Bordeaux, Pessac, France
Correspondence: Chloé James, INSERM U1034, Haut‐Leveque Hospital, Bordeaux University Hospital Center, 1, avenue Magellan, 33600 Pessac, France|Tel.: +33 55 789 1979|E‐mail: chloe.james@inserm.fr
ISTH Academy. James C. May 1, 2019; 273607
Chloé James
Chloé James
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Journal Abstract
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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.
Keyword(s)
blood vessels, Cre recombinase, endothelial cells, hematopoietic system, tamoxifen, transgenic mice
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