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

Binsheng Wang, Lichao Wang, Nathan S. Gasek, Yueying Zhou, Taewan Kim, Chun Guo, Evan R. Jellison, Laura Haynes, Sumit Yadav, Tamar Tchkonia, George A. Kuchel, James L. Kirkland, Ming Xu

Research output: Contribution to journalArticlepeer-review

Abstract

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 p16Ink4a-highly expressing (p16high) cells. In the present technical report, we generated a p21-Cre mouse model, containing a p21 promoter-driving inducible Cre, enabling us to examine p21Cip1-highly expressing (p21high) 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 p21high cells in vivo. We showed that p21high cells can be induced by various conditions, and percentages of p21high cells varied from 1.5% to 10% across different tissues in 23-month-old mice. Intermittent clearance of p21high 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 p21high cells to further understand the biology of senescent cells.

Original languageEnglish (US)
Pages (from-to)962-973
Number of pages12
JournalNature Aging
Volume1
Issue number10
DOIs
StatePublished - Oct 2021

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology
  • Neuroscience (miscellaneous)

Fingerprint

Dive into the research topics of 'An inducible p21-Cre mouse model to monitor and manipulate p21-highly-expressing senescent cells in vivo'. Together they form a unique fingerprint.

Cite this