Epimorphic regeneration in mice is p53-independent

L. Matthew Arthur, Renee M. Demarest, Lise Clark, Dmitri Gourevitch, Kamila Bedelbaeva, Rhonda Anderson, Andrew Snyder, Anthony J. Capobianco, Paul Lieberman, Lionel Feigenbaum, E. Heber-Katz

Research output: Contribution to journalReview article

16 Scopus citations

Abstract

The process of regeneration is most readily studied in species of sponge, hydra, planarian and salamander (i.e., newt and axolotl). The closure of MRL mouse ear pinna through-and-through holes provides a mammalian model of unusual wound healing/regeneration in which a blastema-like structure closes the ear hole and cartilage and hair follicles are replaced. Recent studies, based on a broad level of DNA damage and a cell cycle pattern of G2/M "arrest," showed that p21Cip1/Waf1 was missing from the MRL mouse ear and that a p21-null mouse could close its ear holes. Given the p53/p21 axis of control of DNA damage, cell cycle arrest, apoptosis and senescence, we tested the role of p53 in the ear hole regenerative response. Using backcross mice, we found that loss of p53 in MRL mice did not show reduced healing. Furthermore, cross sections of MRL. p53-/- mouse ears at 6 weeks post-injury showed an increased level of adipocytes and chondrocytes in the region of healing whereas MRL or p21-/- mice showed chondrogenesis alone in this same region, though at later time points. In addition, we also investigated other cell cycle-related mutant mice to determine how p21 was being regulated. We demonstrate that p16 and Gadd45 null mice show little healing capacity. Interestingly, a partial healing phenotype in mice with a dual Tgfβ/Rag2 knockout mutation was seen. These data demonstrate an independence of p53 signaling for mouse appendage regeneration and suggest that the role of p21 in this process is possibly through the abrogation of the Tgfβ/Smad pathway.

Original languageEnglish (US)
Pages (from-to)3691-3697
Number of pages7
JournalCell Cycle
Volume9
Issue number18
DOIs
StatePublished - Sep 15 2010

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Keywords

  • Ear-hole
  • Mouse
  • MRL
  • p21
  • p53
  • Regeneration
  • Tgfβ

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Arthur, L. M., Demarest, R. M., Clark, L., Gourevitch, D., Bedelbaeva, K., Anderson, R., Snyder, A., Capobianco, A. J., Lieberman, P., Feigenbaum, L., & Heber-Katz, E. (2010). Epimorphic regeneration in mice is p53-independent. Cell Cycle, 9(18), 3691-3697. https://doi.org/10.4161/cc.9.18.13119