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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

1
VIB Center for Cancer Biology and KU Leuven Department of Oncology, University of Leuven, 3000 Leuven, Belgium
2
Facultad de Ingeniería y Ciencias Aplicadas, Universidad de Las Americas, 170501 Quito, Ecuador
3
Liver Cell Biology research group, Vrije Universiteit Brussel, 1090 Brussels, Belgium
4
Laboratory of Hepato-gastroenterology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, 1200 Brussels, Belgium
5
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; https://doi.org/10.3390/cells8040380
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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Abstract

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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