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- Title
The role of p21 in regulating mammalian regeneration.
- Authors
Arthur, Larry Matthew; Heber-Katz, Ellen
- Abstract
The MRL (Murphy Roths Large) mouse has provided a unique model of adult mammalian regeneration as multiple tissues show this important phenotype. Furthermore, the healing employs a blastema-like structure similar to that seen in amphibian regenerating tissue. Cells from the MRL mouse display DNA damage, cell cycle G2/M arrest, and a reduced level of p21CIP1/WAF. A functional role for p21 was confirmed when tissue injury in an adult p21-/- mouse showed a healing phenotype that matched the MRL mouse, with the replacement of tissues, including cartilage, and with hair follicle formation and a lack of scarring. Since the major canonical function of p21 is part of the p53/p21 axis, we explored the consequences of p53 deletion. A regenerative response was not seen in a p53-/- mouse and the elimination of p53 from the MRL background had no negative effect on the regeneration of the MRL.p53-/- mouse. An exploration of other knockout mice to identify p21-dependent, p53-independent regulatory pathways involved in the regenerative response revealed another significant finding showing that elimination of transforming growth factor-β1 displayed a healing response as well. These results are discussed in terms of their effect on senescence and differentiation.
- Subjects
REGENERATION (Biology); GENETIC research; TRANSFORMING growth factors-beta; LABORATORY mice; REGENERATIVE medicine; GUIDED tissue regeneration
- Publication
Stem Cell Research & Therapy, 2011, Vol 2, Issue 3, p1
- ISSN
1757-6512
- Publication type
Article
- DOI
10.1186/scrt71