University of Oulu

He, Q., Li, X., Singh, K. et al. The Cdh5-CreERT2 transgene causes conditional Shb gene deletion in hematopoietic cells with consequences for immune cell responses to tumors. Sci Rep 9, 7548 (2019).

The Cdh5-CreERT2 transgene causes conditional Shb gene deletion in hematopoietic cells with consequences for immune cell responses to tumors

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Author: He, Qi1,2; Singh, Kailash3; Luo, Zhengkang3;
Organizations: 1Department of Medical cell Biology, Uppsala University, Uppsala, Sweden
2Cyrus Tang Hematology Center, Soochow University, Suzhou, China
3Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
4Institute of Molecular Genetics of the CAS, Prague, Czech Republic
5Transgenic Animals Facility, Oulu University, Oulu, Finland.
6Department of immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.8 MB)
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Language: English
Published: Springer Nature, 2019
Publish Date: 2020-04-07


The tamoxifen-responsive conditional Cdh5-CreERT2 is commonly used for endothelial cell specific conditional deletion of loxP-flanked gene sequences. To address the role of endothelial cell Shb gene for B16F10 melanoma immune responses, tamoxifen-injected Cdh5-CreERT2/WT and Cdh5-CreERT2/Shbflox/flox mice received subcutaneous tumor cell injections. We observed a decrease of tumor myeloid cell Shb mRNA in the tamoxifen treated Cdh5-CreERT2/Shbflox/flox mice, which was not present when the mice had undergone a preceding bone marrow transplantation using wild type bone marrow. Differences in CD4+/FoxP3+ Tregs were similarly abolished by a preceding bone marrow transplantation. In ROSA26-mTmG mice, Cdh5-CreERT2 caused detectable floxing in certain bone marrow populations and in spleen cells. Floxing in bone marrow could be detected two months after tamoxifen treatment. In the spleen, however, floxing was undetectable two months after tamoxifen treatment, suggesting that Cdh5-CreERT2 is operating in a non-renewable population of hematopoietic cells in this organ. These data suggest that conditional gene deletion in hematopoietic cells is a potential confounder in experiments attempting to assess the role of endothelial specific effects. A cautious approach to achieve an endothelial-specific phenotype would be to adopt a strategy that includes a preceding bone marrow transplantation.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 9
Article number: 7548
DOI: 10.1038/s41598-019-44039-z
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
3111 Biomedicine
Funding: The Shbflox/flox mouse was generated by the support of the Intrafrontier I3 project under the EU contract Grant Agreement Number 312325 of the EC FP7 capacities specific programme. Additional support was provided by the Swedish Research Council (2016-01085), The Swedish Cancer Foundation (150880), Exodiab and the Family Ernfors fund.
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