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
/
Shb
flox/flox
mice received subcutaneous tumor cell injections. We observed a decrease of tumor myeloid cell
Shb
mRNA in the tamoxifen treated
Cdh5-CreERT2
/
Shb
flox/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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.