title: The role of p21 in regulating mammalian regeneration.
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.
authors: The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
authors: Larry Matthew
authors: LM
authors: Arthur
authors: Ellen
authors: E
authors: Heber-Katz
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004260:DNA Repair / Q000235:genetics; D004431:Ear, External / Q000293:injuries / Q000502:physiology; D017353:Gene Deletion; D016158:Genes, p53; D056726:Genetic Association Studies; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D013045:Species Specificity; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000502:physiology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016160:Retinoblastoma Protein; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53