Read by QxMD icon Read

mdx mouse

Robert G Barker, Barnaby P Frankish, Hongyang Xu, Robyn M Murphy
Duchenne muscular dystrophy (DMD) patients and the dystrophic mdx mouse have an elevated demand for ATP requiring processes, including Ca2+ regulation and skeletal muscle regeneration. As a key substrate for cellular ATP production, altered glycogen metabolism may contribute significantly to dystrophic pathology and explain reports of mild glucose intolerance. We compare the soleus and extensor digitorum longus (EDL) muscles of the mdx mouse during active muscle necrosis (at 28 days) and at 70 days where pathology is stable...
March 2018: Physiological Reports
Nora Yucel, Alex C Chang, John W Day, Nadia Rosenthal, Helen M Blau
Duchenne muscular dystrophy (DMD) is a common fatal heritable myopathy, with cardiorespiratory failure occurring by the third decade of life. There is no specific treatment for DMD cardiomyopathy, in large part due to a lack of understanding of the mechanisms underlying the cardiac failure. Mdx mice, which have the same dystrophin mutation as human patients, are of limited use, as they do not develop early dilated cardiomyopathy as seen in patients. Here we summarize the usefulness of the various commonly used DMD mouse models, highlight a model with shortened telomeres like humans, and identify directions that warrant further investigation...
2018: NPJ Regenerative Medicine
Mark A Aminzadeh, Russell G Rogers, Mario Fournier, Rachel E Tobin, Xuan Guan, Martin K Childers, Allen M Andres, David J Taylor, Ahmed Ibrahim, Xiangming Ding, Angelo Torrente, Joshua M Goldhaber, Michael Lewis, Roberta A Gottlieb, Ronald A Victor, Eduardo Marbán
Genetic deficiency of dystrophin leads to disability and premature death in Duchenne muscular dystrophy (DMD), affecting the heart as well as skeletal muscle. Here, we report that clinical-stage cardiac progenitor cells, known as cardiosphere-derived cells (CDCs), improve cardiac and skeletal myopathy in the mdx mouse model of DMD. Injection of CDCs into the hearts of mdx mice augments cardiac function, ambulatory capacity, and survival. Exosomes secreted by human CDCs reproduce the benefits of CDCs in mdx mice and in human induced pluripotent stem cell-derived Duchenne cardiomyocytes...
February 17, 2018: Stem Cell Reports
J Patrick Gonzalez, Jayalakshmi Ramachandran, Eric Himelman, Myriam A Badr, Chifei Kang, Julie Nouet, Nadezhda Fefelova, Lai-Hua Xie, Natalia Shirokova, Jorge E Contreras, Diego Fraidenraich
Duchenne muscular dystrophy (DMD) associated cardiomyopathy remains incurable. Connexin 43 (Cx43) is upregulated and remodeled in the hearts of mdx mice, a mouse model of DMD. Hearts from Wild Type, mdx, and mdx:Cx43(+/-) mice were studied before (4-6 months) and after (10-15 months) the onset of cardiomyopathy to assess the impact of decreasing Cx43 levels on cardiac pathology in dystrophic mice. Increased connexin 43 protein levels in mdx hearts were not observed in mdx:Cx43(+/-) hearts. Cx43 remodeling in mdx hearts was attenuated in mdx:Cx43(+/-) hearts...
February 2, 2018: Neuromuscular Disorders: NMD
Marcel Veltrop, Laura van Vliet, Margriet Hulsker, Jill Claassens, Conny Brouwers, Cor Breukel, Jos van der Kaa, Margot M Linssen, Johan T den Dunnen, Sjef Verbeek, Annemieke Aartsma-Rus, Maaike van Putten
Duchenne muscular dystrophy (DMD) is a severe muscle-wasting disease generally caused by reading frame disrupting mutations in the DMD gene resulting in loss of functional dystrophin protein. The reading frame can be restored by antisense oligonucleotide (AON)-mediated exon skipping, allowing production of internally deleted, but partially functional dystrophin proteins as found in the less severe Becker muscular dystrophy. Due to genetic variation between species, mouse models with mutations in the murine genes are of limited use to test and further optimize human specific AONs in vivo...
2018: PloS One
Joseph X DiMario
Dystrophic skeletal muscle is characterized by fibrotic accumulation of extracellular matrix components that compromise muscle structure, function, and capacity for regeneration. Tissue fibrosis is often initiated and sustained through transforming growth factor β (TGFβ) signaling, and KLF10 is an immediate early gene that is transcriptionally activated in response to TGFβ signaling. It encodes a transcriptional regulator that mediates the effects of TGFβ signaling in a variety of cell types. This report presents results of investigation of the effects of loss of KLF10 gene expression in wild-type and dystrophic (mdx) skeletal muscle...
February 16, 2018: American Journal of Pathology
Nalinda B Wasala, Jin-Hong Shin, Yi Lai, Yongping Yue, Federica Montanaro, Dongsheng Duan
Heart disease is a major health threat for Duchenne/Becker muscular dystrophy patients and carriers. Expression of a 6 to 8-kb mini-dystrophin gene in the heart holds promise to dramatically change the disease course. However the mini-dystrophin gene cannot be easily studied with adeno-associated virus (AAV) gene delivery because the size of the minigene exceeds AAV packaging capacity. We previously studied cardiac protection of the ∆H2-R19 minigene using the cardiac specific transgenic approach. Although this minigene fully normalized skeletal muscle force, it only partially corrected ECG and heart hemodynamics in dystrophin-null mdx mice that had moderate cardiomyopathy...
February 13, 2018: Human Gene Therapy
Leonit Kiriaev, Sindy Kueh, John W Morley, Kathryn N North, Peter J Houweling, Stewart I Head
A striking pathological feature of dystrophinopathies is the presence of morphologically abnormal branched skeletal muscle fibers. The deterioration of muscle contractile function in Duchenne muscular dystrophy is accompanied by both an increase in number and complexity of these branched fibers. We propose that when number and complexity of branched fibers reaches a critical threshold, "tipping point" the branches in and of themselves are the site of contraction-induced rupture. In the present study, we use the dystrophic mdx mouse and littermate controls to study the pre-diseased dystrophic fast-twitch EDL muscle at 2-3-weeks, the peak myonecrotic phase at 6-9 weeks and finally "old" at 58-112 weeks...
February 7, 2018: American Journal of Physiology. Cell Physiology
Sandra Murphy, Margit Zweyer, Michael Henry, Paula Meleady, Rustam R Mundegar, Dieter Swandulla, Kay Ohlendieck
The highly progressive neuromuscular disorder dystrophinopathy is triggered by primary abnormalities in the Dmd gene, which causes cytoskeletal instability and loss of sarcolemmal integrity. Comparative organellar proteomics was employed to identify sarcolemma-associated proteins with an altered concentration in dystrophic muscle tissue from the mdx-4cv mouse model of dystrophinopathy. A lectin agglutination method was used to prepare a sarcolemma-enriched fraction and resulted in the identification of 190 significantly changed protein species...
February 1, 2018: Journal of Proteomics
Elizabeth M Gibbs, Rachelle H Crosbie-Watson
Measuring functional outcomes in the treatment of muscular dystrophy is an essential aspect of preclinical testing. The assessment of voluntary ambulation in mouse models is a non-invasive and reproducible activity assay that is directly analogous to measures of patient ambulation such as the 6-minute walk test and related mobility scores. Many common methods for testing mouse ambulation speed and distance are based on the open field test, where an animal's free movement within an arena is measured over time...
December 29, 2017: Journal of Visualized Experiments: JoVE
Robert G Barker, Victoria L Wyckelsma, Hongyang Xu, Robyn M Murphy
Mitochondrial dysfunction is a pathological feature of Duchenne muscular Dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterised by progressive muscle wasting and weakness. Mitochondria are a source of cellular ATP and involved in Ca2+ regulation and apoptotic signalling. Ameliorating aberrant mitochondrial function has therapeutic potential for reducing DMD disease severity. The dystrophic mdx mouse exhibits peak muscle damage at 21-28d which stabilises after 8 weeks. The amino acid taurine is implicated in mitochondrial health and function, with endogenous concentrations low when measured during the cycle of peak muscle damage in mdx mice...
December 20, 2017: American Journal of Physiology. Cell Physiology
Camilo Riquelme-Guzman, Osvaldo Contreras, Enrique Brandan
Fibrosis is a common feature of several chronic diseases, and is characterized by exacerbated accumulation of extracellular matrix (ECM). Understanding the cellular and molecular mechanisms involved in the development of this condition is crucial for designing efficient treatments for those pathologies. Connective tissue growth factor (CTGF/CCN2) is a pleiotropic protein with strong pro-fibrotic activity. In this report, we present experimental evidence showing that ECM stimulates the synthesis of CTGF in response to lysophosphatidic acid (LPA)...
December 27, 2017: American Journal of Physiology. Cell Physiology
Lulu Huang, Audrey Low, Sagar S Damle, Melissa M Keenan, Steven Kuntz, Susan F Murray, Brett P Monia, Shuling Guo
BACKGROUND: About 11% of all human genetic diseases are caused by nonsense mutations that generate premature translation termination codons (PTCs) in messenger RNAs (mRNA). PTCs not only lead to the production of truncated proteins, but also often result in  decreased mRNA abundance due to  nonsense-mediated mRNA decay (NMD). Although pharmacological inhibition of NMD could be an attractive therapeutic approach for the treatment of diseases caused by nonsense mutations, NMD also regulates the expression of 10-20% of the normal transcriptome...
January 15, 2018: Genome Biology
Lena Rubi, Hannes Todt, Helmut Kubista, Xaver Koenig, Karlheinz Hilber
Duchenne muscular dystrophy (DMD), caused by mutations in the gene encoding for the cytoskeletal protein dystrophin, is linked with severe cardiac complications including cardiomyopathy development and cardiac arrhythmias. We and others recently reported that currents through L-type calcium (Ca) channels were significantly increased, and channel inactivation was reduced in dystrophin-deficient ventricular cardiomyocytes derived from the mdx mouse, the most commonly used animal model for human DMD. These gain-of-function Ca channel abnormalities may enhance the risk of Ca-dependent arrhythmias and cellular Ca overload in the dystrophic heart...
January 2018: Physiological Reports
M Siemionow, J Cwykiel, A Heydemann, J Garcia-Martinez, K Siemionow, E Szilagyi
Over the past decade different stem cell (SC) based approaches were tested to treat Duchenne Muscular Dystrophy (DMD), a lethal X-linked disorder caused by mutations in dystrophin gene. Despite research efforts, there is no curative therapy for DMD. Allogeneic SC therapies aim to restore dystrophin in the affected muscles; however, they are challenged by rejection and limited engraftment. Thus, there is a need to develop new more efficacious SC therapies. Chimeric Cells (CC), created via ex vivo fusion of donor and recipient cells, represent a promising therapeutic option for tissue regeneration and Vascularized Composite Allotransplantation (VCA) due to tolerogenic properties that eliminate the need for lifelong immunosuppression...
January 5, 2018: Stem Cell Reviews
María José Acuña, Daniela Salas, Adriana Córdova-Casanova, Meilyn Cruz-Soca, Carlos Céspedes, Carlos P Vio, Enrique Brandan
The Kallikrein Kinin System (KKS) is a vasoactive peptide system with known functions in the maintenance of tissue homeostasis, renal function and blood pressure. The main effector peptide of KKS is Bradykinin (BK). This ligand has two receptors: a constitutive B2 receptor (B2R), which has been suggested to have anti-fibrotic effects in renal and cardiac models of fibrosis; and the inducible B1 receptor (B1R), whose expression is induced by damage and inflammation. Inflammation and fibrosis are hallmarks of Duchenne muscular dystrophy (DMD), therefore we hypothesized that the KKS may play a role in this disease...
December 17, 2017: Journal of Cell Communication and Signaling
Saleh Omairi, Kwan-Leong Hau, Henry Collin-Hooper, Federica Montanaro, Aurelie Goyenvalle, Luis Garcia, Ketan Patel
Exon skipping mediated by tricyclo-DNA (tc-DNA) antisense oligonucleotides has been shown to induce significant levels of dystrophin restoration in mdx, a mouse model of Duchenne muscular dystrophy. This translates into significant improvement in key disease indicators in muscle, cardio-respiratory function, heart, and the CNS. Here we examine the relationship between muscle fiber type, based on myosin heavy chain (MHC) profile, and the ability of tc-DNA to restore not only dystrophin but also other members of the dystrophin-associated glycoprotein complex (DAPC)...
December 15, 2017: Molecular Therapy. Nucleic Acids
Bao T Le, Abbie M Adams, Susan Fletcher, Stephen D Wilton, Rakesh N Veedu
Locked nucleic acid is a prominent nucleic acid analog with unprecedented target binding affinity to cDNA and RNA oligonucleotides and shows remarkable stability against nuclease degradation. Incorporation of locked nucleic acid nucleotides into an antisense oligonucleotide (AO) sequence can reduce the length required without compromising the efficacy. In this study, we synthesized a series of systematically truncated locked nucleic acid-modified 2'-O-methyl AOs on a phosphorothioate (PS) backbone that were designed to induce skipping exon 23 from the dystrophin transcript in H-2Kb-tsA58 mdx mouse myotubes in vitro...
December 15, 2017: Molecular Therapy. Nucleic Acids
Musarrat Maisha Reza, Chu Ming Sim, Nathiya Subramaniyam, Xiaojia Ge, Mridula Sharma, Ravi Kambadur, Craig McFarlane
Background: Irisin is an exercise induced myokine that is shown to promote browning of adipose tissue and hence, increase energy expenditure. Furthermore, our unpublished results indicate that Irisin improves myogenic differentiation and induces skeletal muscle hypertrophy. Since exercise induced skeletal muscle hypertrophy improves muscle strength, we wanted to investigate if ectopic injection of Irisin peptide improves skeletal muscle function in a mouse model of muscular dystrophy...
November 17, 2017: Oncotarget
Biliana Lozanoska-Ochser, Anna Benedetti, Giuseppe Rizzo, Valeria Marrocco, Rosanna Di Maggio, Piera Fiore, Marina Bouche
Chronic muscle inflammation is a critical feature of Duchenne muscular dystrophy and contributes to muscle fibre injury and disease progression. Although previous studies have implicated T cells in the development of muscle fibrosis, little is known about their role during the early stages of muscular dystrophy. Here, we show that T cells are among the first cells to infiltrate mdx mouse dystrophic muscle, prior to the onset of necrosis, suggesting an important role in early disease pathogenesis. Based on our comprehensive analysis of the kinetics of the immune response, we further identify the early pre-necrotic stage of muscular dystrophy as the relevant time frame for T-cell-based interventions...
March 2018: Journal of Pathology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"