scholarly journals Current Translational Research and Murine Models For Duchenne Muscular Dystrophy

2016 ◽  
Vol 3 (1) ◽  
pp. 29-48 ◽  
Author(s):  
Merryl Rodrigues ◽  
Yusuke Echigoya ◽  
So-ichiro Fukada ◽  
Toshifumi Yokota
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Translational Research ◽  
Murine Models

scholarly journals Mutation-independent Proteomic Signatures of Pathological Progression in Murine Models of Duchenne Muscular Dystrophy

2020 ◽  
Vol 19 (12) ◽  
pp. 2047-2067
Author(s):  
Tirsa L. E. van Westering ◽  
Henrik J. Johansson ◽  
Britt Hanson ◽  
Anna M. L. Coenen-Stass ◽  
Yulia Lomonosova ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Growth ◽  
Differentially Expressed ◽  
Murine Models ◽  
Dystrophic Muscle ◽  
C2c12 Myoblasts ◽  
Experimental Therapies ◽  
Dystrophin Protein ◽  
Upstream Regulators

The absence of the dystrophin protein in Duchenne muscular dystrophy (DMD) results in myofiber fragility and a plethora of downstream secondary pathologies. Although a variety of experimental therapies are in development, achieving effective treatments for DMD remains exceptionally challenging, not least because the pathological consequences of dystrophin loss are incompletely understood. Here we have performed proteome profiling in tibialis anterior muscles from two murine DMD models (mdx and mdx52) at three ages (8, 16, and 80 weeks of age), all n = 3. High-resolution isoelectric focusing liquid chromatography-tandem MS (HiRIEF-LC–MS/MS) was used to quantify the expression of 4974 proteins across all 27 samples. The two dystrophic models were found to be highly similar, whereas multiple proteins were differentially expressed relative to WT (C57BL/6) controls at each age. Furthermore, 1795 proteins were differentially expressed when samples were pooled across ages and dystrophic strains. These included numerous proteins associated with the extracellular matrix and muscle function that have not been reported previously. Pathway analysis revealed multiple perturbed pathways and predicted upstream regulators, which together are indicative of cross-talk between inflammatory, metabolic, and muscle growth pathways (e.g. TNF, INFγ, NF-κB, SIRT1, AMPK, PGC-1α, PPARs, ILK, and AKT/PI3K). Upregulation of CAV3, MVP and PAK1 protein expression was validated in dystrophic muscle by Western blot. Furthermore, MVP was upregulated during, but not required for, the differentiation of C2C12 myoblasts suggesting that this protein may affect muscle regeneration. This study provides novel insights into mutation-independent proteomic signatures characteristic of the dystrophic phenotype and its progression with aging.

scholarly journals Characterization of 65 Epitope-Specific Dystrophin Monoclonal Antibodies in Canine and Murine Models of Duchenne Muscular Dystrophy by Immunostaining and Western Blot

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e88280 ◽  
Author(s):  
Kasun Kodippili ◽  
Lauren Vince ◽  
Jin-Hong Shin ◽  
Yongping Yue ◽  
Glenn E. Morris ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Western Blot ◽  
Murine Models

scholarly journals The pan HDAC inhibitor Givinostat improves muscle function and histological parameters in two Duchenne muscular dystrophy murine models expressing different haplotypes of the LTBP4 gene

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Simonetta Andrea Licandro ◽  
Luca Crippa ◽  
Roberta Pomarico ◽  
Raffaella Perego ◽  
Gianluca Fossati ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Grip Strength ◽  
Muscle Function ◽  
Transforming Growth Factor ◽  
Severe Disease ◽  
Phase Iii ◽  
Insertion Polymorphism ◽  
Murine Models ◽  
Cross Sectional

Abstract Background In the search of genetic determinants of Duchenne muscular dystrophy (DMD) severity, LTBP4, a member of the latent TGF-β binding protein family, emerged as an important predictor of functional outcome trajectories in mice and humans. Nonsynonymous single-nucleotide polymorphisms in LTBP4 gene associate with prolonged ambulation in DMD patients, whereas an in-frame insertion polymorphism in the mouse LTBP4 locus modulates disease severity in mice by altering proteolytic stability of the Ltbp4 protein and release of transforming growth factor-β (TGF-β). Givinostat, a pan-histone deacetylase inhibitor currently in phase III clinical trials for DMD treatment, significantly reduces fibrosis in muscle tissue and promotes the increase of the cross-sectional area (CSA) of muscles in mdx mice. In this study, we investigated the activity of Givinostat in mdx and in D2.B10 mice, two mouse models expressing different Ltbp4 variants and developing mild or more severe disease as a function of Ltbp4 polymorphism. Methods Givinostat and steroids were administrated for 15 weeks in both DMD murine models and their efficacy was evaluated by grip strength and run to exhaustion functional tests. Histological examinations of skeletal muscles were also performed to assess the percentage of fibrotic area and CSA increase. Results Givinostat treatment increased maximal normalized strength to levels that were comparable to those of healthy mice in both DMD models. The effect of Givinostat in both grip strength and exhaustion tests was dose-dependent in both strains, and in D2.B10 mice, Givinostat outperformed steroids at its highest dose. The in vivo treatment with Givinostat was effective in improving muscle morphology in both mdx and D2.B10 mice by reducing fibrosis. Conclusion Our study provides evidence that Givinostat has a significant effect in ameliorating both muscle function and histological parameters in mdx and D2.B10 murine models suggesting a potential benefit also for patients with a poor prognosis LTBP4 genotype.

scholarly journals Dual AAV therapy ameliorates exercise-induced muscle injury and functional ischemia in murine models of Duchenne muscular dystrophy

2013 ◽  
Vol 22 (18) ◽  
pp. 3720-3729 ◽  
Author(s):  
Yadong Zhang ◽  
Yongping Yue ◽  
Liang Li ◽  
Chady H. Hakim ◽  
Keqing Zhang ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Muscle Injury ◽  
Murine Models ◽  
Exercise Induced
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