Arthur Larry Matthew, Heber-Katz Ellen
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Stem Cell Res Ther. 2011 Jun 29;2(3):30. doi: 10.1186/scrt71.
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.
MRL（墨菲罗斯大）小鼠提供了一种独特的成年哺乳动物再生模型，因为多种组织都表现出这种重要的表型。此外，其愈合过程采用了类似于两栖动物再生组织中所见的芽基样结构。MRL小鼠的细胞显示出DNA损伤、细胞周期G2/M期阻滞以及p21CIP1/WAF水平降低。当成年p21基因敲除小鼠的组织损伤表现出与MRL小鼠相匹配的愈合表型时，包括软骨组织的替换、毛囊形成且无瘢痕形成，p21的功能作用得到了证实。由于p21的主要经典功能是p53/p21轴的一部分，我们探究了p53缺失的后果。在p53基因敲除小鼠中未观察到再生反应，并且从MRL背景中消除p53对MRL.p53基因敲除小鼠的再生没有负面影响。对其他基因敲除小鼠的探究以确定参与再生反应的p21依赖性、p53非依赖性调节途径，揭示了另一个重要发现，即消除转化生长因子-β1也显示出愈合反应。本文从它们对衰老和分化的影响方面对这些结果进行了讨论。
