| Lack of p21 expression links cell cycle control and appendage regeneration in mice. | |
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MedLine Citation:
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PMID: 20231440 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Animals capable of regenerating multiple tissue types, organs, and appendages after injury are common yet sporadic and include some sponge, hydra, planarian, and salamander (i.e., newt and axolotl) species, but notably such regenerative capacity is rare in mammals. The adult MRL mouse strain is a rare exception to the rule that mammals do not regenerate appendage tissue. Certain commonalities, such as blastema formation and basement membrane breakdown at the wound site, suggest that MRL mice may share other features with classical regenerators. As reported here, MRL fibroblast-like cells have a distinct cell-cycle (G2/M accumulation) phenotype and a heightened basal and wound site DNA damage/repair response that is also common to classical regenerators and mammalian embryonic stem cells. Additionally, a neutral and alkaline comet assay displayed a persistent level of intrinsic DNA damage in cells derived from the MRL mouse. Similar to mouse ES cells, the p53-target p21 was not expressed in MRL ear fibroblasts. Because the p53/p21 axis plays a central role in the DNA damage response and cell cycle control, we directly tested the hypothesis that p21 down-regulation could functionally induce a regenerative response in an appendage of an otherwise nonregenerating mouse strain. Using the ear hole closure phenotype, a genetically mapped and reliable quantitative indicator of regeneration in the MRL mouse, we show that the unrelated Cdkn1a(tmi/Tyj)/J p21(-/-) mouse (unlike the B6129SF2/J WT control) closes ear holes similar to MRL mice, providing a firm link between cell cycle checkpoint control and tissue regeneration. |
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Authors:
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Khamilia Bedelbaeva; Andrew Snyder; Dmitri Gourevitch; Lise Clark; Xiang-Ming Zhang; John Leferovich; James M Cheverud; Paul Lieberman; Ellen Heber-Katz |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-03-15 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-04-01 Completed Date: 2010-04-28 Revised Date: 2010-10-01 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 5845-50 Citation Subset: IM |
Affiliation:
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Cellular and Molecular Oncogenesis and Gene Expression, The Wistar Institute, Philadelphia, PA 19104, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Apoptosis Cell Cycle / genetics, physiology* Cell Division Cell Proliferation Cyclin-Dependent Kinase Inhibitor p21 / deficiency*, genetics, physiology DNA Damage DNA Repair Extremities / physiology Female G2 Phase Mice Mice, Congenic Mice, Inbred C57BL Mice, Knockout Protein Stability Rad51 Recombinase / metabolism Regeneration / genetics, physiology* Tumor Suppressor Protein p53 / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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GM073226/GM/NIGMS NIH HHS; P30 CA10815/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cdkn1a protein, mouse; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Tumor Suppressor Protein p53; EC 2.7.7.-/Rad51 Recombinase; EC 2.7.7.-/Rad51 protein, mouse |
| Comments/Corrections | |
Comment In:
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Nat Rev Genet. 2010 May;11(5):314
[PMID:
20414985
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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