TY - JOUR
T1 - An inducible p21-Cre mouse model to monitor and manipulate p21-highly-expressing senescent cells in vivo
AU - Wang, Binsheng
AU - Wang, Lichao
AU - Gasek, Nathan S.
AU - Zhou, Yueying
AU - Kim, Taewan
AU - Guo, Chun
AU - Jellison, Evan R.
AU - Haynes, Laura
AU - Yadav, Sumit
AU - Tchkonia, Tamar
AU - Kuchel, George A.
AU - Kirkland, James L.
AU - Xu, Ming
N1 - Funding Information:
We thank colleagues in the UConn Center on Aging for helpful and constructive discussion, Z. Hao for histology services and S. Farkas for administrative assistance. This work was supported in part by the Regenerative Medicine Initiative for Diabetes–Career Development Award from Mayo Clinic (to M.X.), Glenn Foundation for Medical Research and AFAR Grant for Junior Faculty (to M.X.), Robert and Arlene Kogod (to J.L.K.), the Connor Group (to J.L.K.), Robert J. and Theresa W. Ryan (to J.L.K.), the Noaber Foundation (to J.L.K.), Travelers Chair in Geriatrics and Gerontology (to G.A.K.), and National Institutes of Health grants (nos. R37AG013925 (to J.L.K.), P01AG062413 (to J.L.K.), R33AG061456 (to J.L.K., T.T. and G.A.K.), AG063528 (to M.X.), AG066679 (to M.X.) and AG068860 (to M.X.)).
Funding Information:
We thank colleagues in the UConn Center on Aging for helpful and constructive discussion, Z. Hao for histology services and S. Farkas for administrative assistance. This work was supported in part by the Regenerative Medicine Initiative for Diabetes–Career Development Award from Mayo Clinic (to M.X.), Glenn Foundation for Medical Research and AFAR Grant for Junior Faculty (to M.X.), Robert and Arlene Kogod (to J.L.K.), the Connor Group (to J.L.K.), Robert J. and Theresa W. Ryan (to J.L.K.), the Noaber Foundation (to J.L.K.), Travelers Chair in Geriatrics and Gerontology (to G.A.K.), and National Institutes of Health grants (nos. R37AG013925 (to J.L.K.), P01AG062413 (to J.L.K.), R33AG061456 (to J.L.K., T.T. and G.A.K.), AG063528 (to M.X.), AG066679 (to M.X.) and AG068860 (to M.X.)).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85118564116&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85118564116&partnerID=8YFLogxK
U2 - 10.1038/s43587-021-00107-6
DO - 10.1038/s43587-021-00107-6
M3 - Article
AN - SCOPUS:85118564116
SN - 2662-8465
VL - 1
SP - 962
EP - 973
JO - Nature Aging
JF - Nature Aging
IS - 10
ER -