Skin wounds in the MRL/MPJ mouse heal with scar

ArticleinWound Repair and Regeneration 14(1):81-90 · January 2006with27 Reads
DOI: 10.1111/j.1524-475X.2005.00092.x · Source: PubMed
Adult MRL/MpJ mice regenerate cartilage during repair of through-and-through ear punch wounds. However, the ability of this mouse strain to heal isolated cutaneous wounds by regeneration or with scar is unknown. The purpose of this study was to characterize the rate of reepithelialization and collagen architecture in dermal wounds from MRL/MpJ mice compared with C57bl/6 and Balb/c strains. Full-thickness incisional (5 mm) and excisional (2 mm diameter) skin wounds were made on the dorsum of 7-week-old MRL/MpJ, C57bl/6, and Balb/c mice. Ear punch wounds were made simultaneously on each animal. Reepithelialization was complete by 48 hours for incisional skin wounds in each strain. All excisional wounds showed incomplete reepithelialization at 24, 48, and 72 hours. At 14 days, all skin wounds had grossly healed. In contrast to the ear wounds made in C57bl/6 and Balb/c mice, MRL/MpJ ear wounds were completely healed by day 28. Dorsal skin wound sections at 14 and 28 days revealed dense collagen deposition and similar degrees of fibrosis between the three strains of mice. In conclusion, in contrast to wound healing in the ear, MRL/MpJ mouse dorsal cutaneous wounds heal similarly to C57bl/6 and Balb/c mice with dermal collagen deposition and scar formation.
    • "The properties of keratins applied in wound dressings may implicate that increased keratin levels in the MRL/MpJ mouse promote regeneration. On the other hand, it should be underlined that dorsal skin lesions in the MRL/MpJ mouse have been reported to heal with scarring [30]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: The MRL/MpJ mouse is a laboratory inbred strain known for regenerative abilities which are manifested by scarless closure of ear pinna punch holes. Enhanced healing responses have been reported in other organs. A remarkable feature of the strain is that the adult MRL/MpJ mouse retains several embryonic biochemical characteristics, including increased expression of stem cell markers. Results: We explored the transcriptome of the MRL/MpJ mouse in the heart, liver, spleen, bone marrow and ears. We used two reference strains, thus increasing the chances to discover the genes responsible for the exceptional properties of the regenerative strain. We revealed several distinctive characteristics of gene expression patterns in the MRL/MpJ mouse, including the repression of immune response genes, the up-regulation of those associated with retinol metabolism and PPAR signalling, as well as differences in expression of the genes engaged in wounding response. Another crucial finding is that the gene expression patterns in the adult MRL/MpJ mouse and murine neonates share a number of parallels, which are also related to immune and wounding response, PPAR pathway, and retinol metabolism. Conclusions: Our results indicate the significance of retinol signalling and neonatal transcriptomic relics as the distinguishing features of the MRL/MpJ mouse. The possibility that retinoids could act as key regulatory molecules in this regeneration model brings important implications for regenerative medicine.
    Full-text · Article · Dec 2015
    • "Two other phenotypes (articular cartilage regeneration and intraarticular fracture healing) are discussed separately. Ear wound healing Complete closure along with full restoration of all structures of 2-millimeter diameter wounds in the ear pinna (Clark et al., 1998; McBrearty et al., 1998; Kench et al., 1999; Masinde et al., 2001; Gourevitch et al., 2003; Rajnoch et al., 2003; Davis et al., 2005; Beare et al., 2006; Colwell et al., 2006; Metcalfe et al., 2006; Naseem et al., 2007; Fitzgerald et al., 2008; Rai et al., 2012) Digit tip regrowth Digit tip amputated neonatally happened to regrow along with complete structural and functional restoration (including nail) (Han et al., 2005; Chadwick et al., 2007) Peripheral nerve regeneration Higher proximal wound nerve density (Buckley et al., 2011) Alkali-burned cornea Rapid re-epithelialization along with restoration of complete functional capacity of the eye without any loss of corneal transparency (Ueno et al., 2005), Cardiac wound Accelerated healing, increased mitosis, increased function by echo, less collagen deposition along with restoration of the function (Leferovich et al., 2001; Bedelbaeva et al., 2004; Naseem et al., 2007) Articular cartilage regeneration Significant regeneration of full-thickness articular cartilage lesions with maximum restoration of matrix staining and hyaline nature of cartilage (Fitzgerald et al., 2008; Rai et al., 2012) Intraarticular fracture Rapid fracture healing along with decreased cartilage degeneration (Ward et al., 2008) Surgical skin wound Slow re-epithelialization, absence of hair follicles and sebaceous glands (Beare et al., 2006; Colwell et al., 2006; Metcalfe et al., 2006; Buckley et al., 2011) 3. Other mouse strains that exhibit super-healing potential Although being called a super healer mouse (Heydemann, 2012), other strains can also heal cartilage damage. LG/J, which shares 75% of its genome with MRL/MpJ (Murphy and Roths, 1979) and LGXSM-6 which shares 76% of its genome with LG/J (Hrbek et al., 2006) have been shown to possess greater regenerative potential for ear wound healing than SM/J, C57BL/6J and many of the other LGXSM recombinant inbred mouse strains (Rai et al., 2012). "
    [Show abstract] [Hide abstract] ABSTRACT: Mammals rarely regenerate their lost or injured tissues into adulthood. MRL/MpJ mouse strain initially identified to heal full-thickness ear wounds now represents a classical example of mammalian wound regeneration since it can heal a spectrum of injuries such as skin and cardiac wounds, nerve injuries and knee articular cartilage lesions. In addition to MRL/MpJ, a few other mouse strains such as LG/J (a parent of MRL/MpJ) and LGXSM-6 (arising from an intercross between LG/J and SM/J mouse strains) have now been recognized to possess regenerative/healing abilities for articular cartilage and ear wound injuries that are similar, if not superior, to MRL/MpJ mice. While some mechanisms underlying regenerative potential have been begun to emerge, a complete set of biological processes and pathways still needs to be elucidated. Using a panel of healer and non-healer mouse strains, our recent work has provided some insights into the genes that could potentially be associated with healing potential. Future mechanistic studies can help seek the Holy Grail of regenerative medicine. This review highlights the regenerative capacity of selected mouse strains for articular cartilage, in particular, and lessons from other body tissues, in general.
    Full-text · Article · Oct 2014
    • "However, at the end of twentieth century, the MRL/MpJ mouse emerged as a classical example of mammalian regeneration since it can heal ear-wounds (Clark et al. 1998; Metcalfe et al. 2006; Fitzgerald et al. 2008; Rai et al. 2012), surgical wounds (Colwell et al. 2006; Heydemann et al. 2012) and articular cartilage lesions (Fitzgerald et al. 2008; Rai et al. 2012). In addition, DBA/1 (Kench et al. 1999; Li et al. 2001; Masinde et al. 2006) and LG/J (Kench et al. 1999; Li et al. 2001; Masinde et al. 2006; Rai et al. 2012) carry similar regenerative abilities to adulthood. "
    [Show abstract] [Hide abstract] ABSTRACT: Tissue regeneration is a complex trait with few genetic models available. Mouse strains LG/J and MRL are exceptional healers. Using recombinant inbred strains from a LG/J and SM/J (non-healer) intercross, we have previously shown a positive genetic correlation between ear-wound healing, knee cartilage regeneration and protection from osteoarthritis. We hypothesize that a common set of genes operates in tissue healing and articular cartilage regeneration. Taking advantage of archived histological sections from recombinant inbred strains, we analyzed expression of candidate genes through branched-chain DNA technology directly from tissue lysates. We determined broad-sense heritability of candidates, Pearson's correlation of candidates with healing phenotypes, and Ward's minimum variance cluster analysis for strains. A bioinformatic assessment of allelic polymorphisms within and near candidate genes was performed. The expression of several candidates was significantly heritable among strains. While several genes correlated with both ear-wound and cartilage healing at a marginal level, the expression of four genes representing DNA repair (Xrcc2, Pcna) and Wnt signaling (Axin2, Wnt16) pathways was significantly positively correlated with both phenotypes. Cluster analysis accurately classified healers and non-healers for seven out of eight strains based on gene expression. Specific sequence differences between LG/J and SM/J were identified as potential causal polymorphisms. Our study suggests a common genetic basis between tissue healing and osteoarthritis susceptibility. Mapping genetic variations causing differences in diverse healing responses in multiple tissues may reveal generic healing processes in pursuit of new therapeutic targets designed to induce or enhance regeneration and potentially protection from osteoarthritis.
    Full-text · Article · Sep 2013
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