Heart regeneration in adult MRL mice

Leferovich, John; Bedelbaeva, Khamilia; Samulewicz, Stefan; Zhang, Xiang Ming; Zwas, Donna R.; Lankford, Edward B.; Heber‐Katz, Ellen

doi:10.1073/pnas.181329398

Cited by 234 publications

(217 citation statements)

References 40 publications

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“…Since that time, there have been many reports showing that multiple tissue types in MRL mice display healing responses. These include heart myocardium (Leferovich et al, 2001;Haris Naseem et al, 2007;Alfaro et al, 2008), digits (Chadwick et al, 2007;Gourevitch et al, 2009), articular cartilage (Fitzgerald et al, 2008;Rai et al, 2012), intra-articular fractures (Ward et al, 2008), corneal epithelium (Ueno et al, 2005), CNS stem cells and tissue (Hampton et al, 2004;Baker et al, 2006;Balu et al, 2009;Thuret et al, 2009), central and peripheral nerves (Buckley et al, 2011;Thuret et al, 2012) and myometrial healing (Buhimschi et al, 2010). Further, dorsal skin wounds repaired with skin transplants also show enhanced healing without scarring in MRL (Tolba et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

et al. 2014

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External ear hole closure in LG/J mice represents a model of regenerative response. It is accompanied by the formation of a blastema-like structure and the re-growth of multiple tissues, including cartilage. The ability to regenerate tissue is heritable. An F34 advanced intercross line of mice (Wustl:LG,SM-G34) was generated to identify genomic loci involved in ear hole closure over a 30-day healing period. We mapped 19 quantitative trait loci (QTL) for ear hole closure. Individual gene effects are relatively small (0.08 mm), and most loci have co-dominant effects with phenotypically intermediate heterozygotes. QTL support regions were limited to a median size of 2 Mb containing a median of 19 genes. Positional candidate genes were evaluated using differential transcript expression between LG/J and SM/J healing tissue, function analysis and bioinformatic analysis of single-nucleotide polymorphisms in and around positional candidate genes of interest. Analysis of the set of 34 positional candidate genes and those displaying expression differences revealed over-representation of genes involved in cell cycle regulation/DNA damage, cell migration and adhesion, developmentally related genes and metabolism. This indicates that the healing phenotype in LG/J mice involves multiple physiological mechanisms.

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Section: Introductionmentioning

confidence: 99%

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

et al. 2014

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“…The heart, on the other hand, shows little regenerative capacity, and the progressive pathology may be driven instead by a combination of fibrosis and/or cardiomyocyte loss. [11], [12] A better understanding of the molecular and cellular pathogenesis of the heart involvement in DMD would help to identify suitable therapeutic targets that may eventually improve the quality of life and prolong survival in DMD patients.…”

Section: Introductionmentioning

confidence: 99%

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

Spurney

Knoblach

Pistilli

et al. 2008

Neuromuscular Disorders

136

133

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Duchenne muscular dystrophy (DMD; dystrophin-deficiency) causes dilated cardiomyopathy in the second decade of life in affected males. We studied the dystrophin-deficient mouse heart (mdx) using high frequency echocardiography, histomorphometry, and gene expression profiling. Heart dysfunction was prominent at 9-10 months of age and showed significantly increased LV internal diameter (end systole) and decreased posterior wall thickness. This cardiomyopathy was associated with a 30% decrease in shortening fraction. Histologically, there was a 10-fold increase in connective tissue volume (fibrosis). mRNA profiling with RT-PCR validation showed activation of key profibrotic genes, including Nox4 and Lox. The Nox gene family expression differed in mdx heart and skeletal muscle, where Nox2 was specifically induced in skeletal muscle while Nox4 was specifically induced in heart. This is the first report of an altered profibrotic gene expression profile in cardiac tissue of dystrophic mice showing echocardiographic evidence of cardiomyopathy.

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“…We hypothesized that MRL/MpJ mice would exhibit improved bone and cartilage healing after intraarticular fracture, which would lead to reduced severity of posttraumatic OA compared with C57BL/6 mice, a common inbred strain of mice generally used as a control for this strain (17)(18)(19)(20)(21)(22)(23)(24)(25)(26). The severity of OA changes was assessed by measurements of bone density, subchondral bone thickness, histologic cartilage degeneration, and levels of serum cytokines and biomarkers reflective of cartilage degeneration.…”

mentioning

confidence: 99%

Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse

Ward¹,

Furman²,

Huebner³

et al. 2008

Arthritis & Rheumatism

112

127

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Objective. Posttraumatic arthritis is a frequent long-term complication of intraarticular fractures. A model of a closed intraarticular fracture in C57BL/6 mice that progresses to posttraumatic arthritis has been developed. The MRL/MpJ mouse has shown unique regenerative abilities in response to injury. The objective of this study was to determine if the MRL/MpJ mouse is protected from posttraumatic arthritis after intraarticular fractures.Methods. Intraarticular fractures were created in MRL/MpJ mice and C57BL/6 control mice (n ‫؍‬ 16 each). Limbs were analyzed for posttraumatic arthritis 4 and 8 weeks after fracture using microfocal computed tomography bone morphology, subchondral bone thickness evaluation, and histologic evaluation of cartilage degeneration. Serum cytokines and biomarkers were measured after the mice were killed.Results. Intraarticular fractures were successfully created in all 32 mice. In the experimental fractured limbs, C57BL/6 mice had a decrease in bone density, increased subchondral bone thickness, and increased cartilage degeneration compared with normal contralateral control limbs. In the MRL/MpJ mice, no differences in bone density, subchondral bone thickness, or histologic grading of cartilage degeneration were seen between fractured and contralateral control limbs. Cytokine analysis showed lower systemic levels of the proinflammatory cytokine interleukin-1␣ (IL-1␣) and higher levels of the antiinflammatory cytokines IL-4 and IL-10 in the MRL/MpJ mice.Conclusion. This study shows that the MRL/MpJ mouse is relatively protected from posttraumatic arthritis after intraarticular fracture. Further investigation into the mechanism involved in this response will hopefully provide new insight into the pathogenesis, prevention, and treatment of posttraumatic arthritis after intraarticular fracture.

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Heart regeneration in adult MRL mice

Cited by 234 publications

References 40 publications

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line

Dystrophin-deficient cardiomyopathy in mouse: Expression of Nox4 and Lox are associated with fibrosis and altered functional parameters in the heart

Absence of posttraumatic arthritis following intraarticular fracture in the MRL/MpJ mouse

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