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

ABSTRACT: The role of senescent cells has been implicated in various tissue dysfunction associated with aging, obesity, and other pathological conditions. Currently, most transgenic mouse models only target p16 ^Ink4a-highly-expressing (p16 ^high) cells. Here, 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 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 study 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.

SUBMITTER: Wang B 

PROVIDER: S-EPMC8746571 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature