An inducible p21-Cre mouse model to monitor and manipulate p21-highly-expressing senescent cells in vivo

The role of senescent cells has been implicated in various tissue dysfunctions associated with aging, obesity and other pathological conditions. Currently, most transgenic mouse models target only p16^Ink4a-highly expressing (p16^high) cells. In the present technical report, we generated a p21-Cre mouse model, containing a p21 promoter-driving inducible Cre, enabling us to examine p21^Cip1-highly expressing (p21^high) cells, a previously unexplored cell population exhibiting several characteristics typical of senescent cells. By crossing p21-Cre mice with different floxed mice, we managed to monitor, sort, image, eliminate or modulate p21^high cells in vivo. We showed that p21^high cells can be induced by various conditions, and percentages of p21^high cells varied from 1.5% to 10% across different tissues in 23-month-old mice. Intermittent clearance of p21^high cells improved physical function in 23-month-old mice. Our report demonstrates that the p21-Cre mouse model is a valuable and powerful tool for studying p21^high cells to further understand the biology of senescent cells.