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Open AccessTechnical Note

Comparison of the Opn-CreER and Ck19-CreER Drivers in Bile Ducts of Normal and Injured Mouse Livers

VIB Center for Cancer Biology and KU Leuven Department of Oncology, University of Leuven, 3000 Leuven, Belgium
Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Americas, 170501 Quito, Ecuador
Liver Cell Biology research group, Vrije Universiteit Brussel, 1090 Brussels, Belgium
Laboratory of Hepato-gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1200 Brussels, Belgium
Liver and Pancreas Development Unit, de Duve Institute, Université catholique de Louvain, 1200 Brussels, Belgium
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(4), 380;
Received: 4 April 2019 / Revised: 20 April 2019 / Accepted: 23 April 2019 / Published: 25 April 2019
(This article belongs to the Special Issue Hepatic Stem Cells in Liver and Biliary Regeneration)
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Inducible cyclization recombinase (Cre) transgenic mouse strains are powerful tools for cell lineage tracing and tissue-specific knockout experiments. However, low efficiency or leaky expression can be important pitfalls. Here, we compared the efficiency and specificity of two commonly used cholangiocyte-specific Cre drivers, the Opn-iCreERT2 and Ck19-CreERT drivers, using a tdTomato reporter strain. We found that Opn-iCreERT2 triggered recombination of the tdTomato reporter in 99.9% of all cholangiocytes while Ck19-CreERT only had 32% recombination efficiency after tamoxifen injection. In the absence of tamoxifen, recombination was also induced in 2% of cholangiocytes for the Opn-iCreERT2 driver and in 13% for the Ck19-CreERT driver. For both drivers, Cre recombination was highly specific for cholangiocytes since recombination was rare in other liver cell types. Toxic liver injury ectopically activated Opn-iCreERT2 but not Ck19-CreERT expression in hepatocytes. However, ectopic recombination in hepatocytes could be avoided by applying a three-day long wash-out period between tamoxifen treatment and toxin injection. Therefore, the Opn-iCreERT2 driver is best suited for the generation of mutant bile ducts, while the Ck19-CreERT driver has near absolute specificity for bile duct cells and is therefore favorable for lineage tracing experiments. View Full-Text
Keywords: Cre; cholangiocytes; bile duct cells; knockout; mouse liver; lineage tracing; Opn; Ck19 Cre; cholangiocytes; bile duct cells; knockout; mouse liver; lineage tracing; Opn; Ck19

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Lesaffer, B.; Verboven, E.; Van Huffel, L.; Moya, I.M.; van Grunsven, L.A.; Leclercq, I.A.; Lemaigre, F.P.; Halder, G. Comparison of the Opn-CreER and Ck19-CreER Drivers in Bile Ducts of Normal and Injured Mouse Livers. Cells 2019, 8, 380.

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